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Journal articles on the topic 'Innate lymphocyte cells'
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1
Hildreth, Andrew, and Timothy O’Sullivan. "Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection." Viruses 11, no. 3 (March 19, 2019): 272. http://dx.doi.org/10.3390/v11030272.
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Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Recent discoveries have demonstrated that tissue-resident lymphocyte subsets, comprised of innate lymphoid cells (ILCs) and unconventional T cells, have vital roles in the initiation of primary antiviral responses. Via direct and indirect mechanisms, ILCs and unconventional T cell subsets play a critical role in the ability of the immune system to mount an effective antiviral response through potent early cytokine production. In this review, we will summarize the current knowledge of tissue-resident lymphocytes during initial viral infection and evaluate their redundant or nonredundant contributions to host protection or virus-induced pathology.
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Turner, Jan-Eric, Martina Becker, Hans-Willi Mittrücker, and Ulf Panzer. "Tissue-Resident Lymphocytes in the Kidney." Journal of the American Society of Nephrology 29, no. 2 (November 1, 2017): 389–99. http://dx.doi.org/10.1681/asn.2017060599.
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It has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.
3
Chen, Yi-Ling, Clare S. Hardman, Koshika Yadava, and Graham Ogg. "Innate Lymphocyte Mechanisms in Skin Diseases." Annual Review of Immunology 38, no. 1 (April 26, 2020): 171–202. http://dx.doi.org/10.1146/annurev-immunol-082919-093554.
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Innate lymphocyte populations are emerging as key effectors in tissue homeostasis, microbial defense, and inflammatory skin disease. The cells are evolutionarily ancient and carry conserved principles of function, which can be achieved through shared or unique specific mechanisms. Recent technological and treatment advances have provided insight into heterogeneity within and between individuals and species. Similar pathways can extend through to adaptive lymphocytes, which softens the margins with innate lymphocyte populations and allows investigation of nonredundant pathways of immunity and inflammation that might be amenable to therapeutic intervention. Here, we review advances in understanding of innate lymphocyte biology with a focus on skin disease and the roles of commensal and pathogen responses and tissue homeostasis.
4
Wiarda, Jayne E., Julian M. Trachsel, Sathesh K. Sivasankaran, Christopher K. Tuggle, and Crystal L. Loving. "Intestinal single-cell atlas reveals novel lymphocytes in pigs with similarities to human cells." Life Science Alliance 5, no. 10 (August 22, 2022): e202201442. http://dx.doi.org/10.26508/lsa.202201442.
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Lymphocytes can heavily influence intestinal health, but resolving intestinal lymphocyte function is challenging as the intestine contains a vastly heterogeneous mixture of cells. Pigs are an advantageous biomedical model, but deeper understanding of intestinal lymphocytes is warranted to improve model utility. Twenty-six cell types were identified in the porcine ileum by single-cell RNA sequencing and further compared with cells in human and murine ileum. Though general consensus of cell subsets across species was revealed, some porcine-specific lymphocyte subsets were identified. Differential tissue dissection and in situ analyses conferred spatial context, revealing similar locations of lymphocyte subsets in Peyer’s patches and epithelium in pig-to-human comparisons. Like humans, activated and effector lymphocytes were abundant in the ileum but not periphery of pigs, suggesting tissue-specific and/or activation-associated gene expression. Gene signatures for peripheral and ileal innate lymphoid cells newly discovered in pigs were defined and highlighted similarities to human innate lymphoid cells. Overall, we reveal novel lymphocyte subsets in pigs and highlight utility of pigs for intestinal research applications.
5
Meraviglia, Serena, Sary El Daker, Francesco Dieli, Federico Martini, and Angelo Martino. "γδT Cells Cross-Link Innate and Adaptive Immunity inMycobacterium tuberculosisInfection." Clinical and Developmental Immunology 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/587315.
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Protective immunity against mycobacterial infections such asMycobacterium tuberculosisis mediated by interactions between specific T cells and activated antigen presenting cells. To date, many aspects of mycobacterial immunity have shown that innate cells could be the key elements that substantially may influence the subsequent adaptive host response. During the early phases of infection, innate lymphocyte subsets play a pivotal role in this context. Here we summarize the findings of recent investigations onγδT lymphocytes and their role in tuberculosis immunity.
6
Gasteiger, Georg, Saskia Hemmers, Matthew A. Firth, Audrey Le Floc’h, Morgan Huse, Joseph C. Sun, and Alexander Y. Rudensky. "IL-2–dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells." Journal of Experimental Medicine 210, no. 6 (May 6, 2013): 1167–78. http://dx.doi.org/10.1084/jem.20122462.
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The emergence of the adaptive immune system took a toll in the form of pathologies mediated by self-reactive cells. Regulatory T cells (T reg cells) exert a critical brake on responses of T and B lymphocytes to self- and foreign antigens. Here, we asked whether T reg cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of T reg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self–ligands remained largely intact. In contrast, missing-self responses were increased in the absence of T reg cells as the result of heightened IL-2 availability. We found that IL-2 rapidly boosted the capacity of NK cells to productively engage target cells and enabled NK cell responses to weak stimulation. Our results suggest that IL-2–dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2.
7
Gasteiger, Georg, Saskia Hemmers, Paula D. Bos, Joseph C. Sun, and Alexander Y. Rudensky. "IL-2–dependent adaptive control of NK cell homeostasis." Journal of Experimental Medicine 210, no. 6 (May 6, 2013): 1179–87. http://dx.doi.org/10.1084/jem.20122571.
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Activation and expansion of T and B lymphocytes and myeloid cells are controlled by Foxp3+ regulatory T cells (T reg cells), and their deficiency results in a fatal lympho- and myeloproliferative syndrome. A role for T reg cells in the homeostasis of innate lymphocyte lineages remained unknown. Here, we report that T reg cells restrained the expansion of immature CD127+ NK cells, which had the unique ability to up-regulate the IL2Rα (CD25) in response to the proinflammatory cytokine IL-12. In addition, we observed the preferential accumulation of CD127+ NK cells in mice bearing progressing tumors or suffering from chronic viral infection. CD127+ NK cells expanded in an IL-2–dependent manner upon T reg cell depletion and were able to give rise to mature NK cells, indicating that the latter can develop through a CD25+ intermediate stage. Thus, T reg cells restrain the IL-2–dependent CD4+ T cell help for CD127+ immature NK cells. These findings highlight the adaptive control of innate lymphocyte homeostasis.
8
Matic, Sanja, Suzana Popovic, Predrag Djurdjevic, Danijela Todorovic, Natasa Djordjevic, Zeljko Mijailovic, Predrag Sazdanovic, et al. "SARS-CoV-2 infection induces mixed M1/M2 phenotype in circulating monocytes and alterations in both dendritic cell and monocyte subsets." PLOS ONE 15, no. 12 (December 31, 2020): e0241097. http://dx.doi.org/10.1371/journal.pone.0241097.
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Clinical manifestations of SARS-CoV-2 infection range from mild to critically severe. The aim of the study was to highlight the immunological events associated with the severity of SARS-CoV-2 infection, with an emphasis on cells of innate immunity. Thirty COVID-19 patients with mild/moderate symptoms and 27 patients with severe/critically severe symptoms were recruited from the Clinical Center of Kragujevac during April 2020. Flow cytometric analysis was performed to reveal phenotypic and functional alterations of peripheral blood cells and to correlate them with the severity of the disease. In severe cases, the number of T and B lymphocytes, dendritic cells, NK cells, and HLA-DR-expressing cells was drastically decreased. In the monocyte population proportion between certain subsets was disturbed and cells coexpressing markers of M1 and M2 monocytes were found in intermediate and non-classical subsets. In mild cases decline in lymphocyte number was less pronounced and innate immunity was preserved as indicated by an increased number of myeloid and activated dendritic cells, NK cells that expressed activation marker at the same level as in control and by low expression of M2 marker in monocyte population. In patients with severe disease, both innate and adoptive immunity are devastated, while in patients with mild symptoms decline in lymphocyte number is lesser, and the innate immunity is preserved.
9
Sharapova, T. N., E. A. Romanova, L. P. Sashchenko, N. V. Gnuchev, and D. V. Yashin. "Innate immune protein Tag7 stimulates the appearance of cytotoxic NK cells after incubation with lymphocytes." Доклады Академии наук 484, no. 6 (May 23, 2019): 777–80. http://dx.doi.org/10.31857/s0869-56524846777-780.
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Tag7 (PGRP-S) is an innate immune protein that is involved in the antibacterial and antitumor defense and stimulates the maturation of cytotoxic lymphocyte subpopulations. It was found that the incubation of lymphocytes with Tag7 for 3 days promotes the appearance of cytotoxic NK cells that are active against a number of tumor cell lines.
10
Kawabe, Takeshi, and Alan Sher. "Memory-phenotype CD4+ T cells: a naturally arising T lymphocyte population possessing innate immune function." International Immunology 34, no. 4 (December 13, 2021): 189–96. http://dx.doi.org/10.1093/intimm/dxab108.
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Abstract In conventional adaptive immune responses, upon recognition of foreign antigens, naive CD4+ T lymphocytes are activated to differentiate into effector/memory cells. In addition, emerging evidence suggests that in the steady state, naive CD4+ T cells spontaneously proliferate in response to self-antigens to acquire a memory phenotype (MP) through homeostatic proliferation. This expansion is particularly profound in lymphopenic environments but also occurs in lymphoreplete, normal conditions. The ‘MP T lymphocytes’ generated in this manner are maintained by rapid proliferation in the periphery and they tonically differentiate into T-bet-expressing ‘MP1’ cells. Such MP1 CD4+ T lymphocytes can exert innate effector function, producing IFN-γ in response to IL-12 in the absence of antigen recognition, thereby contributing to host defense. In this review, we will discuss our current understanding of how MP T lymphocytes are generated and persist in steady-state conditions, their populational heterogeneity as well as the evidence for their effector function. We will also compare these properties with those of a similar population of innate memory cells previously identified in the CD8+ T lymphocyte lineage.
11
Carrero, Javier A., Boris Calderon, and Emil R. Unanue. "Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes." Journal of Experimental Medicine 203, no. 4 (March 20, 2006): 933–40. http://dx.doi.org/10.1084/jem.20060045.
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Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor–deficient (IFN-αβR−/−) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-αβR+/+. The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection.
12
Pua, Heather H., Ivan Dzhagalov, Mariana Chuck, Noboru Mizushima, and You-Wen He. "A critical role for the autophagy gene Atg5 in T cell survival and proliferation." Journal of Experimental Medicine 204, no. 1 (December 26, 2006): 25–31. http://dx.doi.org/10.1084/jem.20061303.
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Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5−/− chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5−/− CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5−/− CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
13
Maniar, Amudhan, Xiaoyu Zhang, Wei Lin, Brian R. Gastman, C. David Pauza, Scott E. Strome, and Andrei I. Chapoval. "Human γδ T lymphocytes induce robust NK cell–mediated antitumor cytotoxicity through CD137 engagement." Blood 116, no. 10 (September 9, 2010): 1726–33. http://dx.doi.org/10.1182/blood-2009-07-234211.
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AbstractNatural killer (NK) cells are innate effector lymphocytes that control the growth of major histocompatibility complex class I negative tumors. We show here that γδ T lymphocytes, expanded in vitro in the presence isopentenylpyrophosphate (IPP), induce NK cell–mediated killing of tumors that are usually resistant to NK cytolysis. The induction of cytotoxicity toward these resistant tumors requires priming of NK cells by immobilized human immunoglobulin G1 and costimulation through CD137L expressed on activated γδ T lymphocytes. This costimulation increases NKG2D expression on the NK-cell surface, which is directly responsible for tumor cell lysis. Moreover, culturing peripheral blood mononuclear cells with zoledronic acid, a γδ T lymphocyte activating agent, enhances NK-cell direct cytotoxicity and antibody-dependent cellular cytotoxicity against hematopoietic and nonhematopoietic tumors. Our data reveal a novel function of human γδ T lymphocytes in the regulation of NK cell–mediated cytotoxicity and provide rationale for the use of strategies to manipulate the CD137 pathway to augment innate antitumor immunity.
14
Saudemont, A., K. Okkenhaug, and F. Colucci. "p110δ is required for innate immunity to transplantable lymphomas." Biochemical Society Transactions 35, no. 2 (March 20, 2007): 183–85. http://dx.doi.org/10.1042/bst0350183.
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NK cell (natural killer cells) are lymphocytes of innate immunity that kill tumour cells and respond to infections, without prior stimulation. A balance of activating and inhibitory signals regulates NK cell cytotoxicity, but the molecular mechanisms are not fully understood. General inhibitors of PI3K (phosphoinositide 3-kinase) suppress cytotoxicity in human and mouse NK cells. However, which isoforms and how they regulate NK cell activation is unknown, and no data have been published on mice carrying PI3K mutations. p110δ expression is restricted to leucocytes, where it plays central roles in lymphocyte development and signalling. We have used mice carrying a catalytically inactive mutant form of p110δ in order to determine its role in NK cell biology. We show here that p110δ is not required to kill tumour cells, but unexpectedly p110δ mutant mice failed to fully reject transplanted lymphomas. Our results show for the first time a critical role for p110δ in NK cell biology in vivo.
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Schürch, Christian M., Chiara Caraccio, and Martijn A. Nolte. "Diversity, localization, and (patho)physiology of mature lymphocyte populations in the bone marrow." Blood 137, no. 22 (June 3, 2021): 3015–26. http://dx.doi.org/10.1182/blood.2020007592.
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Abstract The bone marrow (BM) is responsible for generating and maintaining lifelong output of blood and immune cells. In addition to its key hematopoietic function, the BM acts as an important lymphoid organ, hosting a large variety of mature lymphocyte populations, including B cells, T cells, natural killer T cells, and innate lymphoid cells. Many of these cell types are thought to visit the BM only transiently, but for others, like plasma cells and memory T cells, the BM provides supportive niches that promote their long-term survival. Interestingly, accumulating evidence points toward an important role for mature lymphocytes in the regulation of hematopoietic stem cells (HSCs) and hematopoiesis in health and disease. In this review, we describe the diversity, migration, localization, and function of mature lymphocyte populations in murine and human BM, focusing on their role in immunity and hematopoiesis. We also address how various BM lymphocyte subsets contribute to the development of aplastic anemia and immune thrombocytopenia, illustrating the complexity of these BM disorders and the underlying similarities and differences in their disease pathophysiology. Finally, we summarize the interactions between mature lymphocytes and BM resident cells in HSC transplantation and graft-versus-host disease. A better understanding of the mechanisms by which mature lymphocyte populations regulate BM function will likely improve future therapies for patients with benign and malignant hematologic disorders.
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Correia, Daniel V., Manuela Fogli, Kelly Hudspeth, Maria Gomes da Silva, Domenico Mavilio, and Bruno Silva-Santos. "Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells." Blood 118, no. 4 (July 28, 2011): 992–1001. http://dx.doi.org/10.1182/blood-2011-02-339135.
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Abstract The success of cancer immunotherapy depends on productive tumor cell recognition by killer lymphocytes. γδ T cells are a population of innate-like lymphocytes endowed with strong, MHC-unrestricted cytotoxicity against tumor cells. This notwithstanding, we recently showed that a large proportion of human hematologic tumors is resistant to γδ peripheral blood lymphocytes (PBLs) activated with specific agonists to the highly prevalent Vγ9Vδ2 TCR. Although this probably constitutes an important limitation to current γδ T cell–mediated immunotherapy strategies, we describe here the differentiation of a novel subset of Vδ2− Vδ1+ PBLs expressing natural cytotoxicity receptors (NCRs) that directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells. We show that Vδ1+ T cells can be selectively induced to express NKp30, NKp44 and NKp46, through a process that requires functional phosphatidylinositol 3-kinase (PI-3K)/AKT signaling on stimulation with γc cytokines and TCR agonists. The stable expression of NCRs is associated with high levels of granzyme B and enhanced cytotoxicity against lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition. Thus, NKp30+ Vδ1+ T cells constitute a novel, inducible and specialized killer lymphocyte population with high potential for immunotherapy of human cancer.
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Rajakariar, Ravindra, Toby Lawrence, Jonas Bystrom, Mark Hilliard, Paul Colville-Nash, Geoff Bellingan, Desmond Fitzgerald, Muhammad M. Yaqoob, and Derek W. Gilroy. "Novel biphasic role for lymphocytes revealed during resolving inflammation." Blood 111, no. 8 (April 15, 2008): 4184–92. http://dx.doi.org/10.1182/blood-2007-08-108936.
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Abstract Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.
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Popovich, Phillip G., Caroline C. Whitacre, and Bradford T. Stokes. "Is Spinal Cord Injury an Autoimmune Disorder?" Neuroscientist 4, no. 2 (March 1998): 71–76. http://dx.doi.org/10.1177/107385849800400203.
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Cross-talk between cells of the nervous and immune systems is an emerging concept in neurotrauma research. Previously, neuroimmunological approaches in brain and spinal cord injury have focused on the functional consequences of macrophage and microglial activation. These cells constitute the natural, or innate, branch of CNS immunity and respond to injury or infection in a nonspecific fashion. Recent evidence, however, has shown that T-lymphocytes may also play a significant role in spinal cord injury. Once activated, T- and B-lymphocytes orchestrate the complex functions of the inflammatory response. Acquired immunity is readily induced against “non-self,” or foreign, antigens, although “self-reactive” lymphocytes are present in normal individuals, providing the potential for the onset of autoimmunity. Trauma to or infection in the CNS may release “self” antigens normally sequestered behind the blood-brain barrier that can trigger lymphocyte activation. This article addresses the potential pathological and physiological implications of lymphocyte activation induced by traumatic spinal cord injury. NEUROSCIENTIST 4:71-76, 1998
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Cumano, Ana, Claire Berthault, Cyrille Ramond, Maxime Petit, Rachel Golub, Antonio Bandeira, and Pablo Pereira. "New Molecular Insights into Immune Cell Development." Annual Review of Immunology 37, no. 1 (April 26, 2019): 497–519. http://dx.doi.org/10.1146/annurev-immunol-042718-041319.
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During development innate lymphoid cells and specialized lymphocyte subsets colonize peripheral tissues, where they contribute to organogenesis and later constitute the first line of protection while maintaining tissue homeostasis. A few of these subsets are produced only during embryonic development and remain in the tissues throughout life. They are generated through a unique developmental program initiated in lympho-myeloid-primed progenitors, which lose myeloid and B cell potential. They either differentiate into innate lymphoid cells or migrate to the thymus to give rise to embryonic T cell receptor–invariant T cells. At later developmental stages, adaptive T lymphocytes are derived from lympho-myeloid progenitors that colonize the thymus, while lymphoid progenitors become specialized in the production of B cells. This sequence of events highlights the requirement for stratification in the establishment of immune functions that determine efficient seeding of peripheral tissues by a limited number of cells.
20
Maxion, Heather K., Wei Liu, Mi-Hyang Chang, and Kathleen A. Kelly. "The Infecting Dose of Chlamydia muridarum Modulates the Innate Immune Response and Ascending Infection." Infection and Immunity 72, no. 11 (November 2004): 6330–40. http://dx.doi.org/10.1128/iai.72.11.6330-6340.2004.
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ABSTRACT Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 104 to 107 inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.
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Sharapova, Tatiana N., Elena A. Romanova, Olga K. Ivanova, Denis V. Yashin, and Lidia P. Sashchenko. "Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells." International Journal of Molecular Sciences 22, no. 13 (June 26, 2021): 6889. http://dx.doi.org/10.3390/ijms22136889.
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The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70–TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Moreover, incubation of PBMCs with Hsp70 leads to an appearance of cytotoxic lymphocyte subpopulations active against the MHC-negative tumor cells. In addition, both the CD4+ T-lymphocytes and CD14+ monocytes are necessary for the Hsp70 signal transduction and a consequent activation of the cytotoxic lymphocytes. We believe that data presented in this study will broaden the views on the involvement of Hsp70 in the antitumor immunity.
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Kunzmann, Volker, Manfred Smetak, Florian Weissinger, Josef Birkmann, Hermann Einsele, and Martin Wilhelm. "Clinical-Scale Combined CD4/CD8 Depletion for Donor Innate Lymphocyte Infusion (DILI)." Blood 108, no. 11 (November 16, 2006): 3657. http://dx.doi.org/10.1182/blood.v108.11.3657.3657.
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Abstract The ability to selectively deplete or enrich cells of specific phenotype by immunomagnetic selection procedures holds significant promise for application in adoptive immunotherapy protocols. In vitro and in vivo studies demonstrated that MHC-independent effector cells of the innate immune system such as natural killer (NK) cells and γδ T cells have potent anti-tumor activity without inducing Graft-versus-Host disease (GvHD). However, current clinical-scale approaches to reduce the risk of GvHD usually use T-cell depletion (such as CD34+ selection or CD3+ depletion). However, both procedures also deplete γδ T cells which may be advantageous in mediating Graft-versus tumor effects and augmenting innate immune response against infections. Here we present a new method for depletion of T cells with potential GvHD reactivity and simultaneously enrichment of innate lymphocytes (NK cells and γδ T cells) from standard leukapheresis products by using a single-step immunomagnetic protocol which efficiently depletes CD4+ and CD8+ αβ T cells under good manufacturing conditions (GMP). Efficiency of CD4+ and CD8+ T cell depletion from (unstimulated) leukapheresis products (n=6) containing up to 2.0 × 1010 white blood cells, was demonstrated by 4-color flow cytometric analysis (mean log depletion of CD4+ cells: 4.12 (3.17–4.9); mean log depletion of CD8+ cells: 3.77 (2.97–4.54)). In addition to efficient depletion of CD4+ and CD8+ cells, immunomagnetic CD4/CD8 depletion resulted in enrichment of NK cells and γδ T cells (mean NK cell recovery: 38%(19–72), mean γδ T cell cell recovery: 50%(34–79)). In vitro assays of the final product demonstrated that NK cells and γδ T cells preserved their proliferative and cytotoxic capacity. We conclude that simultaneous depletion of CD4+ and CD8+ cells is feasible and can be performed in large scale under GMP conditions with sufficient depletion efficacy of αβ T cells and recovery of functionally intact innate effector lymphocytes (NK cells and γδ T cells) for potential use in adoptive immunotherapy studies.
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Halmer, Ramona, Laura Davies, Yang Liu, Klaus Fassbender, and Silke Walter. "The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE." Cellular Physiology and Biochemistry 37, no. 1 (2015): 269–75. http://dx.doi.org/10.1159/000430351.
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Background: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Methods: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. Results: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. Conclusion: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.
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Bystrom, Jonas, Ian Evans, Justine Newson, Melanie Stables, Iqbal Toor, Nico van Rooijen, Mark Crawford, Paul Colville-Nash, Stuart Farrow, and Derek W. Gilroy. "Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP." Blood 112, no. 10 (November 15, 2008): 4117–27. http://dx.doi.org/10.1182/blood-2007-12-129767.
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AbstractNeutralizing injurious stimuli, proinflammatory mediator catabolism, and polymorphonuclear leukocyte (PMN) clearance are determinants of inflammatory resolution. To this, we recently added innate-type lymphocyte repopulation as being central for restoring postinflammation tissue homeostasis with a role in controlling innate immune–mediated responses to secondary infection. However, although macrophages dominate resolution, their phenotype and role in restoring tissue physiology once inflammation abates are unknown. Therefore, we isolated macrophages from the resolving phase of acute inflammation and found that compared with classically activated proinflammatory M1 cells, resolution-phase macrophages (rMs) possess weaker bactericidal properties and express an alternatively activated phenotype but with elevated markers of M1 cells including inducible cyclooxygenase (COX 2) and nitric oxide synthase (iNOS). This phenotype is controlled by cAMP, which, when inhibited, transforms rM to M1 cells. Conversely, elevating cAMP in M1 cells transforms them to rMs, with implications for cAMP in the resolution of systemic inflammation. It transpires that although rMs are dispensable for clearing PMNs during self-limiting inflammation, they are essential for signaling postresolution lymphocyte repopulation via COX 2 lipids. Thus, rM macrophages are neither classically nor alternatively activated but a hybrid of both, with a role in mediating postresolution innate-lymphocyte repopulation and restoring tissue homeostasis.
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Chang, Sook Kyung, Bonnie K. Arendt, Jaime R. Darce, Xiaosheng Wu, and Diane F. Jelinek. "A role for BLyS in the activation of innate immune cells." Blood 108, no. 8 (October 15, 2006): 2687–94. http://dx.doi.org/10.1182/blood-2005-12-017319.
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AbstractB-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) ligand superfamily. Although BLyS costimulates adaptive immune cells, the ability of BLyS to stimulate innate immune cells has not been described. Here, we show that BLyS strongly induces human monocyte survival, and activation as measured by proinflammatory cytokine secretion and up-regulation of costimulatory molecule expression. In addition, monocytes cultured with BLyS differentiated into macrophage-like cells. Regarding BLyS receptor(s) expression, freshly isolated monocytes bound low levels of exogenous BLyS and expressed primarily intracellular TACI, and cell surface TACI levels increased following monocyte activation. Of interest, bone marrow monocytes from some multiple myeloma patients expressed significant levels of cell surface TACI at isolation. Our findings indicate that BLyS plays a role in activating innate immune cells. Moreover, this study may explain more clearly why high BLyS production is often correlated with certain inflammatory autoimmune diseases and B-lymphocyte malignancies.
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Sharapova, Tatiana N., Elena A. Romanova, Olga K. Ivanova, Lidia P. Sashchenko, and Denis V. Yashin. "Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes." Cells 9, no. 12 (December 4, 2020): 2602. http://dx.doi.org/10.3390/cells9122602.
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Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. The appearance of these cytokines in conditioned medium leads to IL-2 cytokine secretion by CD3+CD4+ lymphocytes. In turn, IL-2 facilitates unspecific activation of three cytotoxic cell subpopulations in the PBMC pool: NK (CD16+CD56+), CD3+CD4+ and CD3+CD8+. These subpopulations appear after a certain period of incubation with Tag7 and show toxicity against tumor cells.
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Sharapova, T. N., E. A. Romanova, L. P. Sashchenko, and D. V. Yashin. "Tag7 (PGLYRP1) Can Induce an Emergence of the CD3+CD4+CD25+CD127+ Cells with Antitumor Activity." Journal of Immunology Research 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/4501273.
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We have shown that in the human peripheral blood cells, the innate immunity protein Tag7 can activate a subpopulation of CD3+CD4+CD25+ cells, which have antitumor activity. These cells can induce lysis of HLA-negative tumor cell lines. The Hsp70 stress molecule on the surface of the tumor cells is used as a recognition target, while the Tag7 protein on the lymphocyte membrane acts as a receptor for Hsp70. We have also demonstrated that this subpopulation of the CD4+CD25+ cells is CD127 positive and hence is not the Treg cells. Our data suggest that this subpopulation of cells is identical to the CD4+CD25+ lymphocytes, which are activated in the leukocyte pool by the IL-2 cytokine.
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Widyadi, Elvan Dwi, Yetti Hernaningsih, Endang Retnowati, Ugroseno Ugroseno, and Ryzky Widi Atmaja. "Differentiation T Lymphocyte cells expressing Interleukin-17 Percentage On Healthy Person and Adult Acute Myeloid Leukemia Patient." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 25, no. 2 (April 13, 2019): 228. http://dx.doi.org/10.24293/ijcpml.v25i2.1383.
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Acute Mieloid Leukemia (AML) is a hematologic cause of cancer deaths of 1.2% including a relatively rare disease but by the end of the decade there is an increase in the number of new cases. The immune system in AML is caused by gene mutations giving immunosuppressive effects so that the immune system will be inhibited in eliminating leukemia cells. The immune response of tumors is important to determine the prognosis, development of new cancer immunotherapy as well. One of the subset of lymphocytes T is gdT lymphocyte cell with innate nature, but until now no information is required about gdT cell profile in AML patients. gdT cells have properties as antitumors played by Interferon production g (INF g), and the nature of protumor by interleukin 17 (IL-17). The percentage of lymphocyte T (CD3 +) of AML patients and healthy people did not differ (p = 0.528), indicating, not being activated for proliferation. gdT Lymphocyte cells percentage in healthy people by race, genetic and exposure to the surrounding environment such as infection. Percentage of gdT lymphocyte of AML patients and healthy people was not different from (p = 0.694), showed an immune response by gdT cells Unefected to proliferate. The percentage of gdT llimfocytes expressing the interleukin 17 (gdT17 cells)in patients AML and healthy people did not differ significantly (p = 0.436), this indicates inhibited proliferation.
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Fauriat, Cyril, Alessandro Moretta, Daniel Olive, and Régis T. Costello. "Defective killing of dendritic cells by autologous natural killer cells from acute myeloid leukemia patients." Blood 106, no. 6 (September 15, 2005): 2186–88. http://dx.doi.org/10.1182/blood-2005-03-1270.
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Abstract At the frontier between innate and adaptive immunity, dendritic cells (DCs) secrete numerous cytokines and express costimulatory molecules that initiate or enhance natural killer (NK) and T-lymphocyte responses. NK cells also regulate DC physiology by killing immature DCs (iDCs), thus limiting inflammation and inappropriate T-lymphocyte tolerization. In a previous study, we have reported that NK cells from acute myeloid leukemia patients (AML-NK cells) have deficient natural cytotoxicity receptor (NCR) expression. Herein, we analyzed the consequences of such a defect regarding the regulatory role of AML-NK cells in DC physiology. We show that NK cells display poor cytolytic capacities against DCs derived from healthy donor monocytes or derived from autologous leukemic blasts. These data point to a novel defect in the regulation of adaptive immune responses initiated by DCs in AML patients. This may lead to specific T-lymphocyte tolerization by spontaneous or ex vivo expanded iDCs expressing leukemia-derived antigens. (Blood. 2005;106: 2186-2188)
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Nazmi, Ali, Kristen L. Hoek, Michael J. Greer, Maria B. Piazuelo, Nagahiro Minato, and Danyvid Olivares-Villagómez. "Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation." PLOS ONE 14, no. 7 (July 10, 2019): e0215883. http://dx.doi.org/10.1371/journal.pone.0215883.
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Carty, Shannon A., Gary A. Koretzky, and Martha S. Jordan. "The Role of IL-4 Signaling in CD8+ Innate-Like Lymphocyte Development." Blood 120, no. 21 (November 16, 2012): 2161. http://dx.doi.org/10.1182/blood.v120.21.2161.2161.
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Abstract Abstract 2161 The innate and adaptive arms of the immune system collaborate to protect the host against invading pathogens and perform immune surveillance against malignant transformation. As key effectors of the adaptive immune system, conventional T cells develop in the thymus and exit to the periphery as naïve cells, requiring antigenic stimulation and subsequent differentiation to gain effector functions, such as cytokine secretion or cytolytic activity. In contrast to conventional T cells, non-conventional T lymphocytes possess characteristics of innate immune cells, such as expression of surface markers associated with activation/memory and acquisition of effector function during thymic development, and thus are termed innate-like lymphocytes (ILLs). Recently, an expanded population of CD8+ ILLs was identified in mice with a mutation in the T cell receptor signaling protein SLP-76 (SLP-76 Y145F mice). These CD8+ ILLs are characterized by expression of activation/memory markers CD44 and CD122, the expression of the T-box transcription factor Eomesodermin (Eomes) and rapid production of IFN-γ after ex vivo stimulation. The development of these CD8+ ILLs occurs in a cell-extrinsic manner and requires IL-4. We demonstrate that IL-4 is sufficient to upregulate Eomes expression in wild-type CD8 single-positive (SP) thymocytes in short-term in vitro culture and potentiate CD8+ ILL development in fetal thymic organ culture. Using phospho-flow cytometry, we find that CD8+ ILLs from SLP-76 Y145F mice have increased STAT6 and Akt activation vs. CD8+ non-ILLs. In CD8SP thymocytes deficient in STAT6, Eomes expression is not upregulated in response to IL-4. In addition, we demonstrate that pharmacologic inhibition of Akt in SLP-76 Y145F fetal thymic organ culture blocks CD8+ ILL development and also prevents IL-4 induced Eomes upregulation in WT CD8SP thymocytes. Importantly, we have identified CD8+ ILLs in human fetal thymocytes and umbilical cord blood and found that IL-4 is sufficient to up-regulate Eomes expression in these cells. Taken together, our data suggest that IL-4 signaling via STAT6 and Akt pathways is required for IL-4 induction of Eomes expression and CD8+ ILL development. Understanding signal transduction pathways required for CD8+ ILL development will provide insight into the development of this unique lymphocyte subset that sits at the interface between innate and adaptive immunity and has been identified in human umbilical cord blood. Disclosures: No relevant conflicts of interest to declare.
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Wijeratne, Tissa, Carmela Sales, Rohit Menon, Leila Karimi, and Mihajlo Jakovljevic. "Highlighting the Role of Universally Available and Innate Immune Cell Counts in Acute Ischemic Stroke: A Scoping Review." Sustainability 13, no. 7 (April 6, 2021): 4069. http://dx.doi.org/10.3390/su13074069.
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Stroke is one of the leading causes of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of acute ischemic stroke (AIS), during the index event and the repair process. Research on neurovascular inflammation has created a renewed interest in the use of easily available biomarkers reflective of innate and adaptive immunological changes with potential diagnostic, prognostic, and therapeutic implications particularly in AIS. The current scoping review aimed to assess the significance the neutrophil to lymphocyte (NLR) in AIS and its related complications and explore their association with post-stroke recovery trajectory. The Arksey and O’Malley methodological framework was employed to review the published papers on the neutrophil–lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000–2020 were included in this scoping review. Fifty-three published papers were reviewed. This review’s key finding is that a canonical inflammatory response occurs in the hyperacute, acute, subacute, and chronic stages of stroke. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes) are associated with poorer outcomes during the acute interventions as well as the recovery trajectory. This scoping review’s findings highlights the utility of a systems biology-based approach in stroke care.
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de Pablo, Raul, Jorge Monserrat, Alfredo Prieto, and Melchor Alvarez-Mon. "Role of Circulating Lymphocytes in Patients with Sepsis." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/671087.
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Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.
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Coakley, John Davis, Eamon P. Breen, Ana Moreno-Olivera, Alhanouf I. Al-Harbi, Ashanty M. Melo, Brian O’Connell, Ross McManus, Derek G. Doherty, and Thomas Ryan. "Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis." Vaccines 8, no. 2 (June 17, 2020): 311. http://dx.doi.org/10.3390/vaccines8020311.
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Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA−, CD197+), effector memory (CD45RA−, CD197−), or terminally differentiated (CD45RA+, CD197−). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA+, CD27+), central memory (CD45RA−, CD27+), effector memory (CD45RA−, CD27−), or terminally differentiated (CD45RA+, CD27−). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis.
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Ducimetière, Laura, Giulia Lucchiari, Gioana Litscher, Marc Nater, Laura Heeb, Nicolás Gonzalo Nuñez, Laura Wyss, et al. "Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis." Proceedings of the National Academy of Sciences 118, no. 27 (June 28, 2021): e2026271118. http://dx.doi.org/10.1073/pnas.2026271118.
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The liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and nonredundant action of two innate lymphocyte subpopulations, conventional natural killer cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s), is essential for antimetastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 controls metastatic seeding, whereas cNKs restrain outgrowth. Whereas the killing capacity of trILC1s was not affected by the metastatic microenvironment, the phenotype and function of cNK cells were affected in a cancer type–specific fashion. Thus, individual cancer cell lines orchestrate the emergence of unique cNK subsets, which respond differently to tumor-derived factors. Our findings will contribute to the development of therapies for liver metastasis involving hepatic innate cells.
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Kim, Chang H. "Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids." Cellular & Molecular Immunology 18, no. 5 (April 13, 2021): 1161–71. http://dx.doi.org/10.1038/s41423-020-00625-0.
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AbstractA mounting body of evidence indicates that dietary fiber (DF) metabolites produced by commensal bacteria play essential roles in balancing the immune system. DF, considered nonessential nutrients in the past, is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs. SCFAs act on many cell types to regulate a number of important biological processes, including host metabolism, intestinal functions, and immunity system. This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes. Current information regarding how SCFAs regulate innate lymphoid cells, T helper cells, cytotoxic T cells, and B cells and how these functions impact immunity, inflammation, and allergic responses are discussed.
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Yang, Jie, Ferry Cornelissen, Natalie Papazian, Rogier M. Reijmers, Miriam Llorian, Tom Cupedo, Mark Coles, and Benedict Seddon. "IL-7–dependent maintenance of ILC3s is required for normal entry of lymphocytes into lymph nodes." Journal of Experimental Medicine 215, no. 4 (February 22, 2018): 1069–77. http://dx.doi.org/10.1084/jem.20170518.
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IL-7 is essential for the development and homeostasis of T and B lymphocytes and is critical for neonatal lymph node organogenesis because Il7−/− mice lack normal lymph nodes. Whether IL-7 is a continued requirement for normal lymph node structure and function is unknown. To address this, we ablated IL-7 function in normal adult hosts. Either inducible Il7 gene deletion or IL-7R blockade in adults resulted in a rapid loss of lymph node cellularity and a corresponding defect in lymphocyte entry into lymph nodes. Although stromal and dendritic cell components of lymph nodes were present in normal numbers and representation, innate lymphoid cell (ILC) subpopulations were substantially decreased after IL-7 ablation. Testing lymphocyte homing in bone marrow chimeras reconstituted with Rorc−/− bone marrow confirmed that ILC3s in lymph nodes are required for normal lymphocyte homing. Collectively, our data suggest that maintenance of intact lymph nodes relies on IL-7–dependent maintenance of ILC3 cells.
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Kannan, Yashaswini, Jianhua Yu, Raquel M. Raices, Sudarshan Seshadri, Min Wei, Michael A. Caligiuri, and Mark D. Wewers. "IκBζ augments IL-12– and IL-18–mediated IFN-γ production in human NK cells." Blood 117, no. 10 (March 10, 2011): 2855–63. http://dx.doi.org/10.1182/blood-2010-07-294702.
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Abstract Interferon-γ (IFN-γ) production by natural killer (NK) cells and cytotoxic lymphocytes is a key component of innate and adaptive immune responses. Because inhibitor of κB-ζ (IκBζ), a Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) inducible transcription factor, regulates IFN-γ production in KG-1 cells, we tested IκBζ's role in the classic lymphocyte pathway of IL-12/IL-18–induced IFN-γ. Upon stimulation with IL-12/IL-18, monocyte-depleted human peripheral blood lymphocytes expressed the 79-kDa form of IκBζ and released IFN-γ. CD56+ NK cells were shown to be the IκBζ-producing lymphocyte subpopulation, which also released abundant IFN-γ in response to IL-12/IL-18. Importantly, IκBζ was undetectable in CD56− lymphocytes where IFN-γ release was 10-fold lower. In addition, small interfering RNA knockdown of IκBζ suppressed IFN-γ expression in CD56+ cells. The association of IκBζ with the IFN-γ promoter was documented by chromatin immunoprecipitation. IFN-γ promoter activity from IκBζ overexpression was confirmed by luciferase reporter assay. Finally, IκBζ coprecipitated with p65 and p50 NF-κB in NK cells in response to IL-12/IL-18, suggesting that IκBζ's effects on IFN-γ promoter activity are coregulated by NF-κB. These results suggest that IκBζ functions as an important regulator of IFN-γ in human NK cells, further expanding the class of IκBζ-modulated genes.
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Cąkała-Jakimowicz, Marta, and Monika Puzianowska-Kuznicka. "Towards Understanding the Lymph Node Response to Skin Infection with Saprophytic Staphylococcus epidermidis." Biomedicines 10, no. 5 (April 28, 2022): 1021. http://dx.doi.org/10.3390/biomedicines10051021.
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In individuals with lymphedema, diabetic foot, or other diseases, infections with saprophytes are common. The response of major cell subpopulations in the draining lymph nodes to skin infection with Staphylococcus epidermidis was assessed using the rat model. After massive subepidermal infection, a cytometric evaluation showed an increase in cytotoxic and helper T lymphocytes and major subpopulations of the innate immune response. Three weeks later, signs of inflammation reduction with an increase in the content of memory T helper lymphocytes and effector memory T cytotoxic lymphocytes were observed. After skin re-infection, a rapid response of cytotoxic, helper, and memory T lymphocytes, memory B lymphocytes and plasmablasts, and macrophages was detected. In addition, a reduction in the number of naïve B lymphocytes, activated MHC class II+ cells, and some cells of the innate immune system was observed. T regulatory lymphocyte response after the initial and secondary S. epidermidis skin infection was not detected. The morphometric evaluation showed significant changes in the main cell subpopulations in each functional zone of the node and then confirmed the efficient elimination of the administered antigen, as evidenced by the observations on day 28. Notably, after re-infection, the cellular response did not exceed the level after the initial infection and was reduced in many cell subpopulations. Understanding how the lymph nodes eliminate S. epidermidis can provide valuable insights into creating immunological therapies against infections with saprophytes.
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Antunes, Inês, and George Kassiotis. "Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice." Journal of Virology 84, no. 24 (October 13, 2010): 12564–75. http://dx.doi.org/10.1128/jvi.01559-10.
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ABSTRACT The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virus-neutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.
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Li, Miao, Yue Zhang, Jianhua Lu, Li Li, Huixia Gao, Cuiqing Ma, Erhei Dai, and Lin Wei. "Asymptomatic COVID-19 Individuals Tend to Establish Relatively Balanced Innate and Adaptive Immune Responses." Pathogens 10, no. 9 (August 30, 2021): 1105. http://dx.doi.org/10.3390/pathogens10091105.
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The sharp increase in the proportion of asymptomatic cases and the potential risk of virus transmission have greatly increased the difficulty of controlling the COVID-19 pandemic. The individual immune response is closely associated with clinical outcomes and pathogenic mechanisms of COVID-19. However, the clinical characteristics and immunophenotyping features of immune cells of asymptomatic individuals remain somewhat mysterious. To better understand and predict the disease state and progress, we performed a comprehensive analysis of clinical data, laboratory indexes and immunophenotyping features in 41 patients with SARS-CoV-2 (including 24 asymptomatic cases and 17 symptomatic individuals). Firstly, from the perspective of demographic characteristics, the rate of asymptomatic infection was significantly higher in those with younger age. Secondly, the laboratory test results showed that some indexes, such as CRP (acute phase reaction protein), D-Dimer and fibrinogen (the marker for coagulation) were lower in the asymptomatic group. Finally, symptomatic individuals were prone to establishing a non-protective immune phenotype by abnormally decreasing the lymphocyte count and percentage, abnormally increasing the Th17 percentage and decreasing Treg percentage, which therefore cause an increase in the neutrophil/lymphocyte ratio (NLR), monocytes/lymphocytes ratio (MLR) and Th17/Treg ratio. On the other hand, asymptomatic individuals tended to establish a more effective and protective immune phenotype by maintaining a normal level of lymphocyte count and percentage and a high level of NK cells. At the same time, asymptomatic individuals can establish a relatively balanced immune response through maintaining a low level of monocytes, a relatively low level of Th17 and high level of Treg, which therefore lead to a decrease in MNKR and Th17/Treg ratio and finally the avoidance of excessive inflammatory responses. This may be one of the reasons for their asymptomatic states. This study is helpful to reveal the immunological characteristics of asymptomatic individuals, understand immune pathogenesis of COVID-19 and predict clinical outcomes more precisely. However, owing to small sample sizes, a future study with larger sample size is still warranted.
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Hoyt, Teri R., Erin Dobrinen, Irina Kochetkova, and Nicole Meissner. "B Cells Modulate Systemic Responses to Pneumocystis murina Lung Infection and Protect On-Demand Hematopoiesis via T Cell-Independent Innate Mechanisms when Type I Interferon Signaling Is Absent." Infection and Immunity 83, no. 2 (December 1, 2014): 743–58. http://dx.doi.org/10.1128/iai.02639-14.
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HIV infection results in a complex immunodeficiency due to loss of CD4+T cells, impaired type I interferon (IFN) responses, and B cell dysfunctions causing susceptibility to opportunistic infections such asPneumocystis murinapneumonia and unexplained comorbidities, including bone marrow dysfunctions. Type I IFNs and B cells critically contribute to immunity toPneumocystislung infection. We recently also identified B cells as supporters of on-demand hematopoiesis followingPneumocystisinfection that would otherwise be hampered due to systemic immune effects initiated in the context of a defective type I IFN system. While studying the role of type I IFNs in immunity toPneumocystisinfection, we discovered that mice lacking both lymphocytes and type I IFN receptor (IFrag−/−) developed progressive bone marrow failure following infection, while lymphocyte-competent type I IFN receptor-deficient mice (IFNAR−/−) showed transient bone marrow depression and extramedullary hematopoiesis. Lymphocyte reconstitution of lymphocyte-deficient IFrag−/−mice pointed to B cells as a key player in bone marrow protection. Here we define how B cells protect on-demand hematopoiesis followingPneumocystis lung infection in our model. We demonstrate that adoptive transfer of B cells into IFrag−/−mice protects early hematopoietic progenitor activity during systemic responses toPneumocystisinfection, thus promoting replenishment of depleted bone marrow cells. This activity is independent of CD4+T cell help and B cell receptor specificity and does not require B cell migration to bone marrow. Furthermore, we show that B cells protect on-demand hematopoiesis in part by induction of interleukin-10 (IL-10)- and IL-27-mediated mechanisms. Thus, our data demonstrate an important immune modulatory role of B cells duringPneumocystislung infection that complement the modulatory role of type I IFNs to prevent systemic complications.
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Douglas, Michael R., Karen E. Morrison, Michael Salmon, and Christopher D. Buckley. "Why does inflammation persist: a dominant role for the stromal microenvironment?" Expert Reviews in Molecular Medicine 4, no. 25 (December 9, 2002): 1–18. http://dx.doi.org/10.1017/s1462399402005264.
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Inflammatory responses occur within tissue microenvironments, with functional contributions from both haematopoietic (lymphocytic) cells and stromal cells (including macrophages and fibroblasts). These environments are complex – a compound of many different cell types at different stages of activation and differentiation. Traditional models of inflammatory disease highlight the role of antigen-specific lymphocyte responses and attempt to identify causative agents. However, recent studies have indicated the importance of tissue microenvironments and the innate immune response in perpetuating the inflammatory process. The prominent role of stromal cells in the generation and maintenance of these environments has begun to challenge the primacy of the lymphocyte in regulating chronic inflammatory processes. Sensible enquiries into factors regulating the persistence of inflammatory disease necessitate an understanding of the mechanisms regulating tissue homeostasis and remodelling during inflammation. This article highlights recent insights into the factors regulating dynamic aspects of inflammation, focusing particularly on mononuclear cell infiltrates, their interactions with stromal cells in tissues and the relevance of these interactions to existing and possible future therapies. A key feature of current research has been a growing appreciation that disordered spatial and temporal interactions between infiltrating immune cells and resident stromal cells lie at the heart of disease persistence.
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Oelze, Beatrice, Kirsten Elger, Patrik Schadzek, Laura Burmeister, Anika Hamm, Sandra Laggies, Virginia Seiffart, Gerhard Gross, and Andrea Hoffmann. "The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6." Molecular and Cellular Biochemistry 476, no. 10 (May 29, 2021): 3655–70. http://dx.doi.org/10.1007/s11010-021-04180-8.
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AbstractAs a response to pro-inflammatory signals mesenchymal stem cells (MSCs) secrete agents and factors leading to lymphocyte recruitment, counteracting inflammation, and stimulating immunosuppression. On a molecular level, the signalling mediator TGF-β-activated kinase 1 (TAK1) is activated by many pro-inflammatory signals, plays a critical role in inflammation and regulates innate and adaptive immune responses as well. While the role of TAK1 as a signalling factor promoting inflammation is well documented, we also considered a role for TAK1 in anti-inflammatory actions exerted by activated MSCs. We, therefore, investigated the capacity of lipopolysaccharide (LPS)-treated murine MSCs with lentivirally modulated TAK1 expression levels to recruit lymphocytes. TAK1 downregulated by lentiviral vectors expressing TAK1 shRNA in murine MSCs interfered with the capacity of murine MSCs to chemoattract lymphocytes, indeed. Analysing a pool of 84 secreted factors we found that among 26 secreted cytokines/factors TAK1 regulated expression of one cytokine in LPS-activated murine MSCs in particular: interleukin-6 (IL-6). IL-6 in LPS-treated MSCs was responsible for lymphocyte recruitment as substantiated by neutralizing antibodies. Our studies, therefore, suggest that in LPS-treated murine MSCs the inflammatory signalling mediator TAK1 may exert anti-inflammatory properties via IL-6.
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Altman, Jennie B., Adriana D. Benavides, Rupali Das, and Hamid Bassiri. "Antitumor Responses of Invariant Natural Killer T Cells." Journal of Immunology Research 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/652875.
Full textAbstract:
Natural killer T (NKT) cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT) cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies.
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Hayday, Adrian C., and Pierre Vantourout. "The Innate Biologies of Adaptive Antigen Receptors." Annual Review of Immunology 38, no. 1 (April 26, 2020): 487–510. http://dx.doi.org/10.1146/annurev-immunol-102819-023144.
Full textAbstract:
Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.
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Petrichuk, S. V., T. V. Radygina, D. G. Kuptsova, O. V. Kurbatova, E. L. Semikina, N. N. Murashkin, A. S. Potapov, and A. P. Fisenko. "Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations." Russian Journal of Immunology 25, no. 4 (October 7, 2022): 491–98. http://dx.doi.org/10.46235/1028-7221-1191-eoa.
Full textAbstract:
Nuclear transcription factor B (NF-B) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-B signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices ( 10, remission). The number of cells with NF-B translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-B translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-B in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-B activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-B activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-B activity was elevated only in T-helper cells. The level of NF-B translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from exacerbation/remission states assessed as the NK cell numbers with NF-B translocation showed a good quality of the stratification model (AUC 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-B translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-B activation in lymphocyte populations in the children with IBD and psoriasis.
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Nussbaumer, Oliver, Georg Gruenbacher, Hubert Gander, and Martin Thurnher. "DC-like cell-dependent activation of human natural killer cells by the bisphosphonate zoledronic acid is regulated by γδ T lymphocytes." Blood 118, no. 10 (September 8, 2011): 2743–51. http://dx.doi.org/10.1182/blood-2011-01-328526.
Full textAbstract:
Abstract Bisphosphonates are mainly used for the inhibition of osteoclast-mediated bone resorption but also have been shown to induce γδ T-cell activation. Using IL-2–primed cultures of CD56+ peripheral blood mononuclear cells, we show here that zoledronic acid (zoledronate) could induce IFN-γ production not only in γδ T lymphocytes but, surprisingly, also in natural killer (NK) cells in a manner that depended on antigen-presenting cells, which share properties of inflammatory monocytes and dendritic cells (DCs; here referred to as DC-like cells). In the presence of γδ T lymphocytes, DC-like cells were rapidly eliminated, and NK cell IFN-γ production was silenced. Conversely, in the absence of γδ T lymphocytes, DC-like cells were spared, allowing NK cell IFN-γ production to proceed. γδ T cell–independent NK cell activation in response to zoledronate was because of downstream depletion of endogenous prenyl pyrophosphates and subsequent caspase-1 activation in DC-like cells, which then provide mature IL-18 and IL-1β for the activation of IL-2–primed NK cells. Pharmacologic inhibition of caspase-1 almost abolished IFN-γ production in NK cells and γδ T lymphocytes, indicating that caspase-1–mediated cytokine maturation is the crucial mechanism underlying innate lymphocyte activation in response to zoledronate.
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Poggi, Alessandro, and Maria R. Zocchi. "Immunomodulatory Properties of Mesenchymal Stromal Cells: Still Unresolved “Yin and Yang”." Current Stem Cell Research & Therapy 14, no. 4 (May 23, 2019): 344–50. http://dx.doi.org/10.2174/1574888x14666181205115452.
Full textAbstract:
Mesenchymal stromal cells (MSC) are mesodermal elements characterized by the ability to differentiate into several types of cells present mainly in connective tissues. They play a key function in tissue homeostasis and repair. Furthermore, they exert a strong effect on both innate and adaptive immune response. The main current of thought considers MSC as strong inhibitors of the immune system. Indeed, the first description of MSC immunomodulation pointed out their inability to induce alloimmune responses and their veto effects on mixed lymphocyte reactions. This inhibition appears to be mediated both by direct MSC interaction with immune cells and by soluble factors. Unfortunately, evidence to support this notion comes almost exclusively from in vitro experiments. In complex experimental systems, it has been shown that MSC can exert immunosuppressive effects also in vivo, either in murine models or in transplanted patients to avoid the graft versus host disease. However, it is still debated how the small number of administered MSC can regulate efficiently a large number of host effector lymphocytes. In addition, some reports in the literature indicate that MSC can trigger rather than inhibit lymphocyte activation when a very low number of MSC are co-cultured with lymphocytes. This would imply that the ratio between the number of MSC and immune cells is a key point to forecast whether MSC will inhibit or activate the immune system. Herein, we discuss the conflicting results reported on the immunomodulatory effects of MSC to define which features are relevant to understand their behavior and cross-talk with immune cells.
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Steurer, Martina, Elke Malenke, Birgit Federmann, Lothar Kanz, Wolfgang Andreas Bethge, and Stefan Wirths. "Rapid Reconstitution of Human Antibody Secreting Cells After Haploidentical Allogeneic Stem Cell Transplantation." Blood 114, no. 22 (November 20, 2009): 3682. http://dx.doi.org/10.1182/blood.v114.22.3682.3682.
Full textAbstract:
Abstract Abstract 3682 Poster Board III-618 Innate immunity including granulocytes, monocytes, and NK cells is reported to recover rapidly after allogeneic stem cell transplantation within weeks. In contrast, adaptive immunity, including T- and B-cells, has delayed recovery over months. In murine models innate type marginal zone and B1 B cells, established at fetal age and providing natural antibodies, are distinguished from adaptive B2 or follicular B cells. A crucial maturation and survival factor for adaptive murine B cells was shown to be TNF-family member BAFF (B cell-activating factor), while development of innate B1 B cells is BAFF independent. Kinetics in reconstitution of innate and adaptive immunity after ablation in adults may give insight into hierarchy and attribution to innate and adaptive immunity of defined lymphocyte populations. Reconstitution of lymphopoiesis after CD3 and CD19 depleted haploidentical stem cell transplantation was analyzed in 10 patients, which received monoclonal anti-CD3 antibody OKT3 as immunosuppressant only. This model may enable detailed in vivo evaluation of de novo B cell formation. Weekly samples before and after reduced-intensity conditioning were analyzed by flow cytometry for absolute numbers of T-cell, NK-, and B-cell subsets. Their origin of host or donor hematopoiesis was differentiated by HLA-FACS. Antibody secreting cells (ASC) were enumerated by ELISPOT. Plasma cytokine concentrations were determined by bead based arrays and ELISA. Complete reconstitution of allogeneic NK cells was found at day +21 after transplantation. CD4+ and CD8+ T-cells and their subsets had delayed reconstitution with less then 100 cells/μl at 3 months after transplantation. CD19+ B-lymphocytes of naïve and memory phenotype (>0,5% of all lymphocytes) were detected not before day +60. In contrast, complete reconstitution of antibody-secreting cells after a nadir (<0,05/μl) was observed at day +14. Absolute numbers of ASC were comparable to those of healthy controls (d+14: 72 ASC/μl vs. control: 12 ASC/μl). ASC secreting the isotypes IgM and IgA were more prevalent than IgG compared to controls (time increase: IgM 20; IgA 10; IgG 2,9). These ASC appear CD19low/neg, CD38+, and intracellular Ig+ in flow cytometry and carried donor HLA-haplotype. Reconstitution of ASC occurred without detectable circulating T-cells and before increase of BAFF concentrations were observed. In summary, the rapid and complete reconstitution of peripheral blood ASC after allogeneic transplantation, far proceeding detection of naïve and memory type B-cells, is a novel observation. Incidence before T-cell reconstitution and increase in BAFF concentrations indicates a T-cell and BAFF independent mechanism allocating these early ASC to innate immunity, potentially maintaining natural antibody levels. Disclosures: No relevant conflicts of interest to declare.