Dissertationen zum Thema „CD44 antigen“
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1
Varelias, Antiopi. „Studies of CD44 variant isoform expression and function on activated human peripheral blood mononuclear cells and in renal transplantation“. Title page, summary and contents only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phv293.pdf.
2
Voort, Robbert van der. „Hepatocyte growth factor, Met, and CD44 a ménage à trois in B cells /“. [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/55874.
3
Föger, Niko. „Costimulatory function of CD44 : acting in unison with the T cell receptor“. kostenfrei, 2000. http://nbn-resolving.de/urn/resolver.pl?urn=nbn:de:bvb:20-opus-1186.
4
Lein, Michael Torsten. „Neue Serummarker bei urologischen Malignomen mit dem Schwerpunkt Prostatakarzinom und Anwendung von Proteinase-Inhibitoren in der Therapie des Prostatakarzinoms“. Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2001. http://dx.doi.org/10.18452/13730.
Annotation:
Die vorliegende Habilitationsschrift "Neue Serummarker bei urologischen Malignomen mit dem Schwerpunkt Prostatakarzinom und Anwendung von Proteinase-Inhibitoren in der Therapie des Prostatakarzinoms" faßt Ergebnisse zusammen, die ich in den Jahren von 1996 bis 2000 als Erstautor in wissenschaftlichen Artikeln von peer reviewed Zeitschriften veröffentlicht habe. Zusätzlich werden 14 Arbeiten mit ihren Aussagen eingeschlossen, bei denen ich als Koautor beteiligt war. Gegenstand der Habilitationsschrift sind Untersuchungen zur diagnostischen Optimierung des Tumormarkers Prostataspezifisches Antigen (PSA) und zum Expressionsverhalten von CD44-Proteinen bzw. Matrix-Metalloproteinasen (MMPs) als potentielle, neue Marker bei urologischen Karzinomen. Die nachgewiesene Bedeutung der MMPs bei der Tumorprogression und -metastasierung hat mich dazu veranlaßt, tierexperimentelle Studien zur Hemmung der MMP-Aktivität mit synthetischen Inhibitoren in meine Arbeit aufzunehmen. Zielstellung war hierbei die Evaluierung neuer Therapieoptionen beim fortgeschrittenen Tumor. Im Mittelpunkt der Untersuchungen steht das Prostatakarzinom (PCa) als häufigster maligner Tumor des Mannes. 1. Das PSA ist ohne Zweifel der beste Tumormarker in der Diagnostik des PCa. Der Optimierung dieses Markers wird große Bedeutung zugemessen. Dabei werden verschiedene Konzepte verfolgt, wobei die Bestimmung der Isoformen des PSA die zur Zeit erfolgreichste Richtung zu sein scheint. Die Ergebnisse meiner u.a. im Rahmen von Multizenterstudien durchgeführten Untersuchungen belegen den diagnostischen Nutzen der zusätzlichen Bestimmung des f-PSA%, um PCa-Patienten früher zu erkennen und besser gegenüber Patienten mit benigner Prostatahyperplasie (BPH) abgrenzen zu können. Ein weiteres Ergebnis der Untersuchungen zur diagnostischen Validität anderer PSA-Isoformen ist die Feststellung, daß die Bestimmung des gebundenen PSA keinen Vorteil gegenüber dem f-PSA% hat. Widersprüchliche Angaben in der Literatur konnten damit ausgeräumt werden. Diese Ergebnisse veranlaßten die Firma Roche als Kooperationspartner, die Weiterentwicklung eines ACT-PSA Prototyp-Testsystems einzustellen. Die Ergebnisse meiner Untersuchungen zu den PSA-Isoformen haben inzwischen Eingang in den klinischen Alltag gefunden und werden in der Urologischen Klinik der Charité genutzt. Es wurden Entscheidungsgrenzen für den f-PSA%-Wert zur Indikationsstellung von Stanzbiopsien der Prostata als Klinikstandard erarbeitet. 2. Bei verschiedenen urologischen Tumoren wurde das Expressionsverhalten von CD44-Proteinen und MMPs bzw. deren Inhibitoren bestimmt, um eine mögliche Bedeutung bei der Tumorprogression zu erfassen. Diese Untersuchungen sind gleichzeitig Voraussetzung für eine mögliche Anwendung der Komponenten in der Diagnostik und Therapiekontrolle bei diesen Tumorentitäten. Im Gegensatz zu anderen menschlichen Tumoren konnten bei den untersuchten urologischen Tumoren keine veränderten Serumkonzentrationen der CD44-Proteine einschließlich der Varianten nachgewiesen werden. Daher habe ich weiterführende Studien zu den CD44-Proteinen nicht durchgeführt. 3. Im Tumorgewebe sowie im Plasma von Patienten mit PCa und Nierenzellkarzinom konnte ich signifikante Veränderungen von MMPs und deren Inhibitoren nachweisen. Die Situation im Gewebe spiegelt sich zum Teil im Blut der Patienten wider. Diese Beobachtungen beweisen die Bedeutung der MMPs bei der Tumorprogression und -metastasierung. Prinzipiell kann die Bestimmung einzelner MMPs bzw. TIMPs in der Diagnostik von urologischen Tumoren genutzt werden. Die niedrige Sensitivität in der individuellen Erfassung des einzelnen Tumorpatienten schränkt jedoch die praktische Anwendung ein. 4. Die veränderte MMP-Expression bzw. die Dysbalance zwischen MMPs und TIMPs hat mich veranlaßt, synthetische Inhibitoren zur Blockierung der MMP-Aktivität in einem Standardtiermodell des menschlichen PCa einzusetzen. In einer ersten Untersuchung am Dunning-Tumor der Ratte wurde nachgewiesen, daß dieser Tumor MMP9 exprimiert und die Serumkonzentration mit der Tumorgröße korreliert. In weiteren tierexperimentellen Untersuchungen wurde der Einfluß von Batimastat, einem Breitspektrum-Inhibitor der MMPs und einem neuentwickelten, selektiveren Inhibitor (Icol) auf das orthotope Tumorwachstum ermittelt. Beide Substanzen führten zu einer Hemmung des lokalen Tumorwachstums. Durch Applikation von Icol wurde eine Reduzierung des Tumorgewichtes um 90% im Vergleich zu den unbehandelten Kontrolltieren erreicht. Diese Beobachtungen haben eine doppelte Bedeutung. Zum einen beweist die Hemmwirkung von synthetischen MMP-Inhibitoren im Tiermodell die Funktion der MMPs bei der lokalen Tumorprogression. Zum anderen werden durch diese erfolgreichen tierexperimentellen Studien mit neuen Substanzen Voraussetzungen für die klinische Anwendung bei Patienten mit hormonrefraktärem PCa geschaffen.The aim of my "habilitation thesis" was to evaluate the diagnostic validity of prostate-specific antigen (PSA) in serum and tissue, the serum pattern of CD44 proteins and of the matrix metalloproteinases (MMPs) in serum and tissue of urological malignancies. As MMPs seem to play an important role in tumor progression and metastasis, animal studies were additionally initiated in order to investigate the influence of synthetic inhibitors of MMPs on prostate cancer. 1. PSA is the most important and accurate tumor marker in prostate cancer diagnosis. However, PSA is an organ-specific marker, but is not tumor-specific. Elevated PSA concentrations are seen with non-malignant prostatic diseases like benign prostatic hyperplasia (BPH). Moreover, not all patients with prostate cancer have elevated PSA concentrations. In order to optimize the diagnostic validity of PSA, several concepts have been developed. Determination of the PSA isoforms in serum could help discriminate between prostate cancer and BPH. In various own studies, including a multicenter clinical trial, the determination of free PSA and the calculation the ratio of free PSA to total PSA (fPSA/tPSA) has proven to be a promising tool in prostate cancer diagnosis. Regarding the diagnostic validity of the complexed PSA conflicting data exist. Our results, using a newly developed alpha-1-antichymotrypsin-PSA (ACT-PSA) assay by Roche are contradictory to recent published data. Based on data of a multicenter trial, the determination of ACT-PSA as well as the ACT-PSA to tPSA ratio did not improve the differential diagnostic impact in patients undergoing evaluation for prostate cancer compared to the ratio fPSA/tPSA. 2. In various malignant diseases characteristic alterations in the expression of CD44 proteins and their variants have been observed. In contrast to those observations in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for detecting and staging patients with urological malignant tumors. Therefore, further investigation have not been performed. 3. Matrix-metalloproteinases (MMP) form a group of endogenous proteases with the common ability to degrade various components of the extracellular matrix. It could be demonstrated that increased levels of MMP are associated with the invasive and metastatic potential in human malignant tumors. However, little is known about the role of MMPs in renal cell carcinoma. In own study significant changes of MMP expression have been observed. Although changes in specific MMPs might be characteristic for renal carcinoma tissues and might be partly reflected in the blood, data shown that even MMP-9 as the best plasma marker, had a low sensitivity in detecting renal cell carcinoma. Increased concentrations of MMP-9 in tumor tissue may have important implications for the therapeutic potential of synthetic inhibitors of MMPs. 4. The importance of inhibitors of MMPs in cancer has been demonstrated in various studies. In own investigations, altered levels of MMPs and their specific inhibitors have been elucidated in prostate cancer. Therefore, a study to evaluate the efficacy of synthetic MMP inhibitors (batimastat, Icol) in a standard prostate cancer animal model was performed. Previously, the high expression of MMP-9 in this prostate cancer (Dunning tumor) compared with normal prostatic tissue could be demonstrated. Batimastat and the newly developed inhibitor Icol reduced the orthotopic tumor weights up to 90% in a dose-dependent manner. This results confirmed the importance of MMPs and their inhibitors in tumor progression. It can be concluded that selective inhibition of MMP activity is a novel therapeutic approach, which bears promise for studies in patients with hormone-refractory prostate cancer.
5
Bernardi, Maria Auxiliadora. „Expressão de CD44 e CD24 em carcinomas mamários ductais invasivos de acordo com análise dos subtipos moleculares e sua relação com fatores prognósticos“. Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-27102011-172419/.
Annotation:
Carcinomas de mama são heterogêneos e consistem de diversos tipos celulares. Perfis de expressão gênica usando DNA microarrays identificaram quatro subtipos moleculares fundamentais baseados na expressão de receptores hormonais (estrógeno e progesterona) e de fator de crescimento epidérmico (HER2) (luminal tipo A, luminal tipo B, tumores expressando somente HER2 e triplos negativos) refletindo a heterogeneidade molecular dos carcinomas. Sugeriu-se que esta heterogeneidade advém da presença de células tronco tumorais com a capacidade de se diferenciar ao longo de vias divergentes e outros estudos sugeriram que a presença destas células tronco tumorais pode ser evidenciada pela análise fenotípica de CD44 e CD24. Nosso objetivo foi detectar a freqüência de CD24 e CD44 isolados ou combinados, analisados por imunoistoquímica e sua associação com os subtipos moleculares e com diversos marcadores biológicos em 95 casos de carcinoma ductal infiltrativo organizados em um microarranjo tissular (TMA). Realizamos determinações imunoistoquímicas de CD44, CD24, citoqueratinas (CK5, CK6, CK18), claudina 7 e Ki67. Subgrupos moleculares foram definidos pela expressão imunoistoquímica de RE, RP e HER2. Resultados: Os tumores apresentaram uma maior freqüência dos grupos luminais (49,5%) atribuído à alta expressão de RP ou RE (47,4%), e freqüência menor de tumores triplo negativos (21,5%) e HER2 (9,5%). Os fenótipos CD44+CD24- e CD44-/CD24+ estavam respectivamente presentes em 8,4% e 16,8% dos tumores e o fenótipo duplamente positivo foi predominante (45,3%). Ausência de ambas as proteínas foi evidente em 6,3% dos tumores. Tumores com fenótipo CD44+CD24- (definido como um marcador de células tronco tumorais por estudos in vitro) foram mais comuns em tumores triplos negativos mas não demonstraram nenhum tipo de associação com características clinico-patológicas e demais marcadores. Este fenótipo não foi expresso nos tumores HER2 positivos. O fenótipo duplamente positivo CD44+CD24+ mostrou-se mais freqüente nos subtipos luminais ou com alta expressão de HER2. Os fenótipos (CD44-CD24+ e CD44-CD24-) não mostraram associação com os subgrupos. Tumores expressando CD24+ isolado, com grande freqüência deste marcador (74,7%), mostraram significativa associação com positividade do RE, RP e Ki67 e uma significância marginal com marcadores de diferenciação luminal (CK18 e claudina 7, p = 0,14). Nenhuma associação foi observada com tumores CD44+ quando analisado isoladamente. A expressão de claudina 7 e Ki67 não mostrou associação com os subgrupos e a expressão de CK5 apresentou uma tendência a uma maior negatividade nos subtipos luminais e uma freqüência maior de positividade nos tumores HER2 e triplo negativos. De outro lado, associação da freqüência da expressão positiva de CK18 nos subgrupos luminais foi estatisticamente significativa (p = 0,003). Para se determinar se CD24+ e CD44+ e seus subtipos combinados poderiam afetar a sobrevida global e o intervalo livre da doença preparamos curvas de sobrevida de acordo com Kaplan-Meier que foram analisadas estatisticamente (log rank test). A mediana do período de seguimento das pacientes do nosso estudo foi de 4,8 anos (0,36 10,9 anos). Estas análises não demostraram influência dos fenótipos CD44+CD24- ou CD44+ sobre a sobrevida global ou intervalo livre de doença, mas observamos uma tendência a um prognóstico mais favorável. Interessantemente tumores HER2 positivos não expressaram este fenótipo, sugerindo que outros marcadores de células tronco caracterizam estes tumores. O fenótipo CD44-CD24+ mostrou-se mais freqüente nos tumores luminais, mas não apresentou correlação com marcadores clínico-patológicos ou biológicos analisados. Não houve diferenças significativas com respeito a sobrevida global ou intervalo livre de doença . A expressão de CD24+ isolado associou-se a expressão dos marcadores de diferenciação celular e a uma diminuição do intervalo livre de doença. A sobrevida livre de doença (10 anos) indicou uma percentagem de 94,1% para CD24- e 72,1% para os pacientes CD24+ enquanto a sobrevida global foi de 84,2% para os pacientes CD24- e 72,1% para os pacientes CD24+. Citoqueratinas (CK5, CK18) e Ki67 não influenciaram a sobrevida e o intervalo livre de doença. No entanto a expressão positiva de claudina 7, embora não associada à sobrevida global, foi estatisticamente associada ao decréscimo do intervalo livre da doença (p = 0,05). Conclusão: As características dos tumores CD44+CD24- e sua tendência a associação um prognóstico mais favorável parecem não estar de acordo com as propriedades descritas na literatura para células tronco e enfatizam a necessidade de outros marcadores. A determinação da freqüência de CD44+ e claudina 7 positiva pode contribuir para a análise do prognóstico em carcinoma de mamaBackground: Breast carcinomas consist phenotypically of diverse cells and exhibit intra tumoral heterogeneity being stratified in several subgroups based in gene expression profiles or histochemical biomarkers. It was suggested that this heterogeneity is derived in part from the transformation of different subsets of cancer stem cells (CSC) in each intrinsic subgroup. The presence of CSC can be evidenced by phenotypic analysis of CD44 e CD24. This study aimed to identify the CD24 and CD44 immunophenotype within invasive ductal breast carcinoma (IDC) subtypes and determine its influence on prognosis as well as its association with the expression of Ki67, citokeratins (CK5, CK6 and CK18) and claudin-7. Methods: Immuno expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). The association with intrinsic subgroups defined as luminal A (ER+, PR+, HER2-), luminal B (ER and or PR+, HER2+), HER2 subtype (ER-, PR-, HER2+) and triple negative (ER-, PR-, HER2-), and the other markers and prognosis was analyzed. Results: CD44+CD24- and CD44-CD24+ were respectively presents in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD44+CD24+ was determined in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44+CD24- phenotype was more common in the basal subgroups but the frequency of this subtype has not been associated with clinical characteristic or biological markers. The phenotype was absent in HER2 tumors whereas luminal tumors are enriched in CD44-CD24+ and CD44+CD24+ cells which did not show associations with clinical/biological markers features. There was also no significant association of the subtypes with the event free (DFS) and overall survival (OS) but the CD44+CD24- phenotype showed a more favorable prognostic as compared to CD44-CD44+ phenotype that showed a worse prognosis (p = 0.26) (median follow up, 4.8 years) CD44+ alone was evident in 57.9%, while CD24+ was positive in 74.7% of the tumors, the latter showing a significant association with ER, PR and Ki67 and a marginal association with CK18 and claudin-7. Expression of claudin-7 and Ki67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found. CD44+ was not significantly associated with OS (p = 0.684) and DFS (p = 0.386) whereas CD24+ expression was also no significantly associated with OS (p = 0.32) but was associated with a decrease in DFS (p = 0.07). CK5, CK18 and Ki67 expression had no influence in OS or DFS, however claudin-7 positive although not statistically associated with OS, was associated with reduced DFS (p = 0.05). Conclusions: The heterogeneity of cells with several CD44CD24 expression may indicate the presence of different stem cell populations. Ocurrence of CD44+CD24- phenotype is more common in triple negative tumors and lower in tumors of luminal type and absent in HER2 tumors. Although not associated significantly with patho-biological markers or OS and DFS, the CD44+CD24- phenotype has a tendency to be a favorable prognostic marker in breast cancer raising the possibilty that the putative tumorigenic ability may no be restricted to cells of this phenotype. The presence of CD44-CD24+ may indicat a worse prognosis. CD24+ was associated with ER, PR, Ki67and showed a marginal association with CK18 and claudin-7. CD24 and Claudin-7 positivity were the only biological markers associated with reduced DFS. These two investigated markers can be used to improve the assessement of prognosis in breast cancer
6
Haas, Karen Marie. „Induction and regulation of bovine B lymphocyte responses /“. free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9999290.
7
Schmitz, Paul. „Mechanismen immunologischer Toleranz nach Lebertransplantation : Untersuchungen zum Zytokinmuster intrahepatischer CD4+ CD45RCpos und CD4+ CD45RCneg T-Lymphozyten“. Doctoral thesis, kostenfrei, 2007. http://nbn-resolving.de/urn/resolver.pl?urn=nbn:de:bvb:20-opus-26703.
8
Giordanengo, Valérie. „Glycoproteines lymphocytaires, infection vih et autoimmunite“. Aix-Marseille 2, 1996. http://www.theses.fr/1996AIX20652.
9
Saeland, Sem. „Caractérisation et physiologie in vitro des cellules hématopoïétiques humaines exprimant l'antigène CD34“. Lyon 1, 1992. http://www.theses.fr/1992LYO1H053.
10
Rose, Charlotte S. P. „CD4 antigen chimaeras of poliovirus“. Thesis, University of Reading, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240217.
11
Haas, Karen M. „Induction and regulation of bovine B lymphocyte responses“. free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9999290.
12
郑健 und Jian Zheng. „Generation of human allo-antigen specific CD4+ and CD8+ regulatory T cells with CD40-activated B cells“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46922969.
13
Mischke, Dirk. „Generierung regulatorischer T-Zellen aus naiven CD4+-CD45RA+-T-Zellen durch Anti-CD4-Interaktion“. Berlin wvb, Wiss. Verl, 2007. http://www.wvberlin.de/data/inhalt/mischke_dirk.html.
14
Li, Ming 1957. „Generation of CD8+ T cell immunity with help from CD4+ T cells“. Monash University, Dept. of Pathology and Immunology, 2002. http://arrow.monash.edu.au/hdl/1959.1/8476.
15
Barton, Gregory Methven. „Positive selection of CD4 T cells by specific peptide-MHC class II complexes /“. Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/4994.
16
Schubert, Lisa Ann. „Characterization of the transcriptional regulation of the human CD40L gene in CD4 T cells /“. Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/8325.
17
Garcia, Alexandre Simões. „Valor prognóstico da imunoexpressão de podoplanina e de CD44v6 na recidiva locorregional dos pacientes com câncer de lábio“. Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-05092017-203930/.
Annotation:
O objetivo deste estudo consistiu em avaliar a expressão imuno-histoquímica da podoplanina e do CD44v6 pelas células malignas, verificando a associação destas proteínas com as variáveis clínicas, microscópicas, com o índice histopatológico de malignidade e com a sobrevivência livre de doença de 91 pacientes portadores de carcinomas espinocelulares (CEC) de lábio inferior, tratados no Centro de Tratamento e Pesquisa do Hospital do Câncer A.C.Camargo, São Paulo. Os tumores foram corados, separadamente, com os anticorpos anti-podoplanina e anti-CD44v6, sendo avaliada a imunoexpressão destas proteínas pelas células neoplásicas, no front de invasão tumoral, por meio de um método semi-quantitativo de escores. A associação da expressão da podoplanina e do CD44v6 com as variáveis demográficas, clínicas e microscópicas foi feita pelo teste do qui-quadrado ou exato de Fisher. As taxas de sobrevivência livre de doença, acumuladas em cinco e dez anos, foram calculadas pelo teste de Kaplan-Meier e a influência das variáveis clínicas e microscópicas no prognóstico avaliadas pelo modelo de regressão de Cox. A correlação entre a podoplanina e o CD44v6 foi analisada pelo teste de Spearman. Em todos os testes estatísticos utilizou-se um nível de significância de 5%. Os resultados mostraram uma predominância da forte expressão membranosa e citoplasmática da podoplanina pelas células malignas. Verificou-se uma associação significativa da podoplanina citoplasmática com a recidiva locorregional (p=0,028) e da podoplanina membranosa com o índice histopatológico de malignidade tumoral (p=0,026). O CD44v6 foi fortemente expresso pelas células neoplásicas de 95,4% dos CECs e significativamente, associado com o estadiamento clínico T (p=0,034). Não houve correlação entre a podoplanina e o CD44v6 nos CECs de lábio inferior. A forte expressão de podoplanina membranosa (p=0,016) e citoplasmática (p=0,030) pelas células malignas foi fator de prognóstico favorável independente na sobrevivência livre de doença. Concluímos que a podoplanina e o CD44v6 são fortemente expressos pelas células neoplásicas e que a forte imunoexpressão membranosa e citoplasmática da podoplanina pode auxiliar na identificação do risco de recidiva locorregional nos pacientes portadores de carcinoma espinocelular de lábio inferior.The aim of this study was evalute the podoplanin and CD44v6 immunohistochemical expression by malignant cells and its association with the clinical and microscopic variables, tumor histopathological grading and disease-free survival of 91 patients with lip squamous cell carcinomas (SCC), submitted to surgical treatment at Research and Treatment Center of the Cancer Hospital A.C. Camargo, São Paulo. The tumors were stained separately, with the antibodies anti-podoplanin and anti-CD44v6, and the immunoexpression of these proteins, by the neoplastic cells in the invasion front, was evaluated by a semi-quantitative scores method. Chi-square test or Fishers exact test was used to analyze the association of podoplanin and CD44v6 expression with demographic, clinical, and microscopic variables. Disease-free survival in five and ten years, were calculated by the Kaplan-Meier method and the influence of clinical and microscopic variables on prognosis were evaluated by the Cox regression model. The correlation between podoplanin and CD44v6 expression was analyzed by Spearman\'s test and a significance level of 5% was used in all statistical tests. The results showed a predominance of strong membranous and cytoplasmic podoplanin expression by malignant cells. An association between cytoplasmic podoplanin and locorregional recurrence (p=0,028) and membranous podoplanin with tumor histopathological grading (p=0,026). CD44v6 was strongly expressed in 95.4% of the SCCs neoplastic cells and significantly associated with the clinical staging T (p=0,034). There was no correlation between podoplanin and CD44v6 expression in the lower lip SCC. The strong expression of membranous (p=0.016) and cytoplasmic (p=0.030) podoplanin by malignant cells was a favorable independent prognostic factor in disease-free survival. Concluding, the podoplanin and CD44v6 are strongly expressed by neoplastic cells and the strong membranous and cytoplasmic immunoexpression of podoplanin can help the identification of locoregional recurrence risk in patients with squamous cell carcinoma of the lower lip.
18
Wheeler, Paul Richard. „Characterisation of T cell anergy in allo-antigen specific CD4⺠cells“. Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288516.
19
Rossmanith, Tanja. „Kultivierung von CD34+-Zellen aus Nabelschnurblut zur Ex-vivo-Expansion von Stamm- und Vorläuferzellen und Untersuchungen zu deren Homing-Fähigkeiten“. [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=96362525X.
20
Müller, Marguerite. „Bestimmung der Verweildauern von 111In-markierten anti-CD66 und anti-CD45 Antikörpern im Rahmen der Konditionierung vor Blutstammzelltransplantation“. [S.l. : s.n.], 2009. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-66243.
21
Stone, John David. „T-cell antigen receptor signal transduction in CD45-null thymocytes“. Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627126.
22
Kennedy, Colleen. „A study of size and compositional heterogeneity of membrane rafts of CD4+ T cells“. Click here for download, 2008. http://proquest.umi.com/pqdweb?did=1568973711&sid=1&Fmt=2&clientId=3260&RQT=309&VName=PQD.
23
Bridoux, Lucie Charpentier Emmanuelle. „Effet de l'inhibiteur tissulaire des métalloprotéinases-1 (TIMP-1) dans les cellules érythroïdes normales et cancéreuses humaines. Caractérisation du récepteur“. Reims : S.C.D. de l'Université, 2009. http://scdurca.univ-reims.fr/exl-doc/GED00001015.pdf.
24
Goupille, Caroline. „Commutation fucose/acide sialique au niveau d'un variant du CD44 : conséquences sur le comportement de cellules de carcinome colique“. Nantes, 1997. http://www.theses.fr/1997NANT04VS.
25
Rogers, Paul R. „Analysis of CD45 Alternative Exon Expression in Murine and Human CD4+ T Cell Subpopulations: a Thesis“. eScholarship@UMMS, 1993. http://escholarship.umassmed.edu/gsbs_diss/282.
Annotation:
Leukocytes express a family of high molecular weight glycoproteins called leukocyte common antigens (CD45) which have tyrosine phosphatase activity and are involved in phosphotyrosine signal transduction. Antibodies to different CD45 isoforms distinguish functionally different CD4+ T cell subsets in humans, rats, and mice. Selected protein isoforms are expressed through a process of exon splicing which is cell-type and differentiation-state specific. Splicing of the three variable exons, A, B, and C, which encode amino acids located near the extracellular amino terminus of the protein, potentially results in generation of eight different mRNA transcripts. The purpose of this study was to determine the relative levels of all eight different CD45 transcripts present in a panel of murine CD4+ T cell lines and normal murine and human CD4+ T cell subsets separated with antibodies to CD45 variable exons. I show, as expected, that the broad features of CD45 surface isoform expression in these cells can be accounted for by the relative amounts of the eight differentially spliced transcripts. Unexpectedly, all the differences in CD45 isoform expression among the CD4+ T cell subpopulations that I measured could be accounted for by differences in the overall level of variable exon expression. I did not see differences among T cell populations in the relative expression of particular variable exons. Exon B was always found in greater abundance than exons C or A. Of the dual exon species, only AB and BC were found in CD4+ T cells. The AC species was undetectable. Human CD4+ T cells, especially those in the naive subset, express higher levels of CD45 variable exons than murine CD4+ T cells.
In unrelated studies, I have generated a rat-mouse hybridoma which secretes a rat IgG antibody reactive with mouse CD45. I show that the monoclonal antibody, 25D10, defines a novel epitope consistent with a post-translational modification of CD45, similar but distinct from the epitope recognized by monoclonal antibody RA3.6B2 (anti-B220). This conclusion is based on evidence that it precipitates similar molecular weight bands from cells as does a framework monoclonal antibody to CD45, yet has a distinct cell surface expression as determined by flow cytometric analysis. It stains activated Th cell lines at a higher intensity than resting Th cells, stains 60-70% of splenocytes, and 25-30% of lymph node cells. It stains all class II positive cells but not freshly isolated CD4+, CD8+ T cells or CD45 transfected fibroblasts.
26
Yin, Liusong. „Studies of HLA-DM in Antigen Presentation and CD4+ T Cell Epitope Selection: A Dissertation“. eScholarship@UMMS, 2014. http://escholarship.umassmed.edu/gsbs_diss/700.
Annotation:
Antigen presented to CD4+ T cells by major histocompatibility complex class II molecules (MHCII) plays a key role in adaptive immunity. Antigen presentation is initiated by the proteolytic cleavage of pathogenic or self proteins and loading of resultant peptides to MHCII. The loading and exchange of peptides to MHCII is catalyzed by a nonclassical MHCII molecule, HLA-DM (DM). It is well established that DM promotes peptide exchange in vitro and in vivo. However, the mechanism of DM-catalyzed peptide association and dissociation, and how this would affect epitope selection in human responses to infectious disease remain unclear. The work presented in this thesis was directed towards the understanding of mechanism of DM-mediated peptide exchange and its role in epitope selection.
In Chapter II, I measured the binding affinity, intrinsic dissociation half-life and DM-mediated dissociation half-life for a large set of peptides derived from vaccinia virus and compared these properties to the peptide-specific CD4+ T cell responses. These data indicated that DM shapes the peptide repertoire during epitope selection by favoring the presentation of peptides with greater DM-mediated kinetic stability, and DM-susceptibility is a strong and independent factor governing peptide immunogenicity.
In Chapter III, I computationally simulated peptide binding competition reactions and found that DM influences the IC50 (50% inhibition concentration) of peptides based on their susceptibility to DM, which was confirmed by experimental data. Therefore, I developed a novel fluorescence polarization-based method to measure DM-susceptibility, reported as a IC50 (change in IC50 in the absence and presence of DM). Traditional assays to measure DM-susceptibility based on differential peptide dissociation rates are cumbersome because each test peptide has to be individually labeled and multiple time point samples have to be collected. However, in this method developed here only single probe peptide has to be labeled and only single reading have to be done, which allows for fast and high throughput measure of DM-susceptibility for a large set of peptides.
In Chapter IV, we generated a series of peptide and MHCII mutants, and investigated their interactions with DM. We found that peptides with non-optimal P1 pocket residues exhibit low MHCII affinity, low kinetic stability and high DM-susceptibility. These changes were accompanied with conformational alterations detected by surface plasmon resonance, gel filtration, dynamic light scattering, small-angle X-ray light scattering, antibody-binding, and nuclear magnetic resonance assays. Surprisingly, all these kinetic and conformational changes could be reversed by reconstitution with a more optimal P9 pocket residue. Taken together, our data demonstrated that conformation of MHCII-peptide complex constrained by interactions throughout the peptide binding groove is a key determinant of DM-susceptibility.
B cells recognizing cognate antigen on the virion can internalize and process the whole virion for antigen presentation to CD4+ T cells specific for an epitope from any of the virion proteins. In turn, the epitope-specific CD4+ T cells provide intermolecular (also known as noncognate or heterotypic) help to B cells to generate antibody responses against any protein from the whole virion. This viral intermolecular help model in which CD4+ T cells provide help to B cells with different protein specificities was established in small size influenza virus, hepatitis B virus and viral particle systems. For large and complex pathogens such as vaccinia virus and bacteria, the CD4+ T cell-B cell interaction model may be complicated because B cells might not be able to internalize the large whole pathogen. Recently, a study in mice observed that CD4+ T cell help is preferentially provided to B cells with the same protein specificity to generate antibody responses against vaccinia virus. However, for larger pathogens such as vaccinia virus and bacteria the CD4+ T cell-B cell interaction model has yet to be tested in humans. In Chapter V, I measured in 90 recently vaccinated and 7 long-term vaccinia-immunized human donors the CD4+ T cell responses and antibody responses against four vaccinia viral proteins (A27L, A33R, B5R and L1R) known to be strongly targeted by cellular and humoral responses. We found that there is no direct linkage between antibody and CD4+ T cell responses against each protein. However, the presence of immune responses against these four proteins is linked together within donors. Taken together, our data indicated that individual viral proteins are not the primary recognition unit and CD4+ T cells provide intermolecular help to B cells to generate robust antibody responses against large and complicated vaccinia virus in humans.
27
Behrendt, Anne. „Differential antigen dependency of CD4+ and CD8+ T cells“. Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-171521.
28
Jellison, Evan Robert. „CD4 T Cell-Mediated Lysis and Polyclonal Activation of B Cells During Lymphocytic Choriomeningitis Virus Infection: A Dissertation“. eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/349.
Annotation:
CD4 T cells and B cells are cells associated with the adaptive immune system. The adaptive immune system is designed to mount a rapid antigen-specific response to pathogens by way of clonal expansions of T and B cells bearing discrete antigen-specific receptors. During viral infection, interactions between CD4 T cells and B cells occur in a dynamic process, where B cells that bind to the virus internalize and degrade virus particles. The B cells then present viral antigens to virus-specific CD4 T cells that activate the B cells and cause them to proliferate and differentiate into virus-specific antibody-secreting cells. Yet, non-specific hypergammaglobulinemia and the production of self-reactive antibodies occur during many viral infections, and studies have suggested that viral antigen-presenting B cells may become polyclonally activated by CD4 T cells in vivo in the absence of viral engagement of the B cell receptor. This presumed polyclonal B cell activation associated with virus infection is of great medical interest because it may be involved in the initiation of autoimmunity or contribute to the long-term maintenance of B cell memory.
In order to directly examine the interactions that occur between T cells and B cells, I asked what would happen to a polyclonal population of B cells that are presenting viral antigens, if they were transferred into virus-infected hosts. I performed these studies in mice using the well-characterized lymphocytic choriomeningitis virus (LCMV) model of infection. I found that the transferred population of antigen-presenting B cells had two fates. Some antigen-expressing B cells were killed in vivo by CD4 T cells in the first day after transfer into LCMV-infected hosts. However, B cells that survived the cytotoxicity underwent a dynamic polyclonal activation manifested by proliferation, changes in phenotype, and antibody production.
The specific elimination of antigen-presenting B cells following adoptive transfer into LCMV-infected hosts is the first evidence that MHC class II-restricted killing can occur in vivo during viral infection. This killing was specific, because only cells expressing specific viral peptides were eliminated, and they were only eliminated in LCMV-infected mice. In addition to peptide specificity, killing was restricted to MHC class II high cells that expressed the B cell markers B220 and CD19. Mice depleted of CD4 T cells prior to adoptive transfer did not eliminate virus-specific targets, suggesting that CD4 T cells are required for this killing. I found that CD4 T cell-dependent cytotoxicity cannot be solely explained by one mechanism, but Fas-FasL interactions and perforin are mechanisms used to induce lysis.
Polyclonal B cell activation, hypothesized to be the cause of virus-induced hypergammaglobulinemia, has never been formally described in vivo. Based on previous studies of virus-induced hypergammaglobulinemia, which showed that CD4 T cells were required and that hypergammaglobulinemia was more likely to occur when virus grows to high titer in vivo, it was proposed that the B cells responsible for hypergammaglobulinemia may be expressing viral antigens to virus-specific CD4 T cells in vivo. CD4 T cells would then activate the B cells. However, because the antibodies produced during hypergammaglobulinemia are predominantly not virus-specific, nonvirus-specific B cells must be presenting viral antigens in vivo.
In my studies, the adoptively transferred B cells that survived the MHC class II-restricted cytotoxicity became polyclonally activated in LCMV-infected mice. Most of the surviving naïve B cells presenting class II MHC peptides underwent an extensive differentiation process involving both proliferation and secretion of antibodies. Both events required CD4 cells and CD40/CD40L interactions to occur but B cell division did not require MyD88-dependent signaling, type I interferon signaling, or interferon γ signaling within B cells. No division or activation of B cells was detected at all in virus-infected hosts in the absence of cognate CD4 T cells and class II antigen. B cells taken from immunologically tolerant donor LCMV carrier mice with high LCMV antigen load became activated following adoptive transfer into LCMV-infected hosts, suggesting that B cells can present sufficient antigen for this process during a viral infection. A transgenic population of B cells presenting viral antigens was also stimulated to undergo polyclonal activation in LCMV-infected mice. Due to the high proportion of B cells stimulated by virus infection and the fact that transgenic B cells can be activated in this manner, I conclude that virus-induced polyclonal B cell activation is independent of B cell receptor specificity. This approach, therefore, formally demonstrates and quantifies a virus-induced polyclonal proliferation and differentiation of B cells which can occur in a B cell receptor-independent manner.
By examining the fate of antigen-presenting B cells following adoptive transfer into LCMV-infected mice, I have been able to observe dynamic interactions between virus-specific CD4 T cells and B cells during viral infection. Adoptive transfer of antigen-presenting B cells results in CD4 T cell-mediated killing and polyclonal activation of B cells during LCMV infection. Studies showing requirements for CD4 T cells or MHC class II to control viral infections must now take MHC class II-restricted cytotoxicity into account. Polyclonal B cell activation after viral infection has the potential to enhance the maintenance of B cell memory or lead to the onset of autoimmune disease.
29
Zilch, Christian Frank. „The control of alternative splicing of the leucocyte common antigen (CD45)“. Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287198.
30
Matthes, Constanze. „Immunmodulation Dendritischer Zellen durch Sekretionsprodukte mesenchymaler Stammzellen mit besonderem Focus auf hCyr61/CCN1“. Doctoral thesis, kostenfrei, 2008. http://nbn-resolving.de/urn/resolver.pl?urn=nbn:de:bvb:20-opus-28129.
31
Khuseyinova, Natalie. „Association between plasma levels of the soluble CD14 receptor of lipopolysaccharide and the C(-260)T polymorphism in the promoter of the CD14 gene and coronary artery disease: investigations in a large case-control study“. Ulm : Universität Ulm, Medizinische Fakultät, 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB9967025.
32
Védrine, Mégane. „Rôle de l'antigène O dans la reconnaissance d'Escherichia coli par les cellules épithéliales mammaires bovines et modulation par le CD14 soluble“. Thesis, Tours, 2019. http://www.theses.fr/2019TOUR4002.
Annotation:
Les mammites constituent la première source de pertes financières des cheptels bovins laitiers en France et dans le monde. Parmi les agents pathogènes des infections mammaires, Escherichia coli (E. coli) représente la bactérie majeure impliquée dans les cas de mammites cliniques aigues. La part des facteurs de l’hôte dans la capacité à éliminer le pathogène causal est en partie avérée, tandis que le lien entre caractéristiques bactériennes et sévérité de l’infection est plus délicat à établir. Cette étude s’attache donc à déterminer les facteurs bactériens importants dans les interactions entre E. coli et la glande mammaire, et en particulier dans la reconnaissance des bactéries par les cellules épithéliales mammaires (CEM) qui constituent l'une des premières lignes de défense de la glande mammaireMastitis constitute the main source of financial losses for dairy herds in France and worldwide. Among major mastitis pathogens Escherichia coli (E. coli) is of great importance, especially in acute clinical mastitis. The role of host factors in the ability to eliminate the causative pathogen is well-known, but the implication of bacterial characteristics in the severity of the infection is more difficult to establish. This study aimed at deciphering the bacterial factors involved in the interactions between E. coli and the mammary gland, and in particular the recognition of E. coli by bovine mammary epithelial cells (MEC), which constitute one of the first defense lines of the mammary gland
33
Pelletier, Ludivine. „Un nouveau rôle pour CD44 dans la transformation cellulaire“. Lyon 1, 2006. http://www.theses.fr/2006LYO10103.
Annotation:
La protéine d’adhérence CD44 est exprimée de façon aberrante dans plusieurs types de cancers mais les mécanismes moléculaires par lesquels elle participe à la tumorigénèse restent mal définis. Le modèle couramment retenu lui attribue un rôle dans la capacité métastatique, un évènement tardif de la tumorigénèse. L’utilisation d’un système original qui mime une activation inductible et réversible de l’oncogène RET dans des fibroblastes de rat, nous a permis de montrer que CD44 participe également aux étapes plus précoces du développement tumoral. L’augmentation d’expression de CD44 au cours de la transformation cellulaire s’accompagne d’un clivage protéolytique séquentiel par des métalloprotéases puis des γ-sécrétases, qui conduit à la translocation nucléaire de son fragment cytoplasmique (CD44-ICD). De manière remarquable, CD44-ICD possède une activité transformante et contribue au processus de transformation induit par RET. Ce travail révèle ainsi une nouvelle fonction pour cD44 dans le développement tumoral via la libération de CD44-ICDThe adhesion protein CD44 is overexpressed in several type of cancer. The mechanisms by which CD44 plays a role in tumor progression are not yet clear, although they may promote metastasis. Using a reversible RET-dependent oncogenic conversion model and a restricted proteomic approach, we identified a positive correlation between the neoplastic transformation and the expression of standard CD44. We found that CD44 is sequentially cleaved by metalloproteases and γ-secretase, resulting in a nuclear translocation of CD44 intracellular domain (CD44-ICD). We showed that this proteolytic fragment possesses a transforming activity and that it participated to RET-induced transformation of RAT-1 cells. This work indicates a novel role for CD44 in early events in tumorigenesis through the relaease of CD44-ICD
34
Dong, Qing. „Mechanisms of CD4+ T cell apoptosis and the role of ethanol as a cofactor in HIV pathogenesis“. Lexington, Ky. : [University of Kentucky Libraries], 2000. http://lib.uky.edu/ETD/ukynusi2000d00003/ThesisQD.pdf.
Annotation:
Thesis (Ph. D.)--University of Kentucky, 2000.Title from document title page. Document formatted into pages; contains vi, 137 p. : ill. Includes abstract. Includes bibliographical references (p. 108-135).
35
Müller, Nicole. „Entwicklung antigenabhängig aktivierbarer TNF-Ligand-Fusionsproteine“. kostenfrei, 2009. http://www.opus-bayern.de/uni-wuerzburg/volltexte/2009/3648/.
36
Bridoux, Lucie. „Effet de l’inhibiteur tissulaire des métalloprotéinases-1 (TIMP-1) dans les cellules érythroïdes normales et cancéreuses humaines. Caractérisation du récepteur“. Reims, 2009. http://theses.univ-reims.fr/exl-doc/GED00001015.pdf.
Annotation:
En dehors de son activité inhibitrice de MMPs, le TIMP-1 présente d'autres activités biologiques telles que des effets mitogéniques et anti-apoptotiques sur différentes lignées cellulaires. Nous avons montré que le TIMP-1 induit la survie des cellules érythroleucémiques humaines UT-7 en activant la voie JAK2/PI 3-kinase/Akt. Récemment, nous avons montré que le TIMP-1 se fixe à une pro-MMP-9 localisée à la membrane plasmique des cellules UT-7 et que l'expression membranaire de la pro-MMP-9 est nécessaire à l'effet anti-apoptotique du TIMP-1. Dans une première partie, nous montrons que CD44 permet l'ancrage de la pro-MMP-9 à la surface cellulaire et que cette protéine joue un rôle crucial dans l'effet anti-apoptotique du TIMP-1 puisque si l'on éteint l'expression de CD44, la pro-MMP-9 n'est plus localisée à la surface cellulaire et le TIMP-1 n'est plus capable d'induire la survie cellulaire. Dans la signalisation anti-apoptotique du TIMP-1, JAK2 est la première tyrosine kinase qui est phosphorylée suite à une stimulation par le TIMP-1. Dans une deuxième partie, nous avons étudié l'interaction entre CD44 et la tyrosine kinase JAK2. Nous montrons que CD44 est associée de manière constitutive à JAK2 et que cette interaction se fait via le domaine FERM de JAK2. D'autres kinases pourraient intervenir dans la signalisation anti-apoptotique du TIMP-1, parmi lesquelles les Src kinases. Dans une troisième partie, nous avons étudié l'implication de la Src kinase Lyn dans l'effet anti-apoptotique du TIMP-1. Nous montrons que la Src kinase Lyn joue un rôle crucial dans l'effet anti-apoptotique du TIMP-1 en amont de la PI 3-kinaseBesides its ability to inhibit MMP activity, TIMP-1 exhibits other biological functions such as mitogenic and anti-apoptotic effects on various cell lines. We showed that TIMP-1 induced UT-7 erythroid cell survival through activation of the JAK2/PI 3-kinase/Akt pathway. Recently, we showed that TIMP-1 specifically bound to pro-MMP-9 localized at the UT-7 plasmic membrane and that pro-MMP-9 membrane expression is crucial for TIMP-1 anti-apoptotic effect. In a first part, we showed that CD44 anchored pro-MMP-9 at the cell surface and that this protein played a crucial role in TIMP-1 anti-apoptotic effect since CD44 silencing abrogated pro-MMP-9 cell surface localisation and enabled TIMP-1-mediated cell survival. In TIMP-1 anti-apoptotic signalling pathway, JAK2 is the first tyrosin kinase phosphorylated following TIMP-1 stimulation. In a second part, we studied the interaction between CD44 and tyrosin kinase JAK2. We showed that CD44 is associated in a constitutive manner to JAK2 via the JAK2 FERM domain. Other kinases could be implicated in TIMP-1 anti-apoptotic pathway, among them the Src kinases. In a third part, we studied the implication of Lyn Src kinase in TIMP-1 effect. We showed that Lyn played a crucial role in TIMP-1 anti-apoptotic effect upstream the PI 3-kinase
37
Grégoire, Claude. „Caractérisation de récepteurs T solubles obtenus par génie génétique“. Aix-Marseille 2, 1991. http://www.theses.fr/1991AIX22018.
Annotation:
Grace aux techniques de genie genetique et de transfert genique, nous avons pu solubiliser le recepteur a l'antigene d'une cellule t cytotoxique. La strategie utilisee consiste a produire des molecules chimeres entre ce recepteur a l'antigene et les immunoglobulines. Ce recepteur t soluble peut egalement servir a generer des anticorps monoclonaux
38
Zhou, Gang. „Mechanisms of CD4+ T cell anergy induced by tumor antigen“. Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080806.
39
Cameron, Thomas O. (Thomas Owen) 1972. „Characterizing antigen-specific CD4⁺ T cells using HLA-DR oligomers“. Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/16808.
Annotation:
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002.Vita.
Includes bibliographical references (leaves 152-165).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
T cells are activated by the engagement of their surface T cell receptors (TCR) by antigenic peptide bound to major histocompatibility complex (MHC). The success or failure of this TCR to MHC-peptide interaction determines the specificity of T cell action, and thus plays a central role in proper immune function. In this thesis, soluble oligomers of MHC-peptide complex were used to investigate several aspects of the T cell immune response. Soluble fluorescent oligomers of human class II MHC were produced and used to detect CD4+ T cells of particular specificities. The critical parameters of this interaction were determined, and differing behaviors of various T cell clones were observed. The implications of these results are discussed, and MHC oligomers are suggested as powerful tools for the investigation T cell avidity modulation. Using a novel methodology for the analysis of the antigen-specific TCR repertoire which includes identification by MHC oligomers, T cells specific for a peptide derived from influenza were isolated, cloned and sequenced. This pool of sequences was observed to be extremely diverse in both VP usage and CDR3 sequence. These results are discussed with regard to the TCR repertoire, structural aspects of TCR/MHC-peptide interaction, and future studies of TCR repertoire analysis. Other studies investigating the triggering mechanism of TCR are summarized and implications of these results for various models of transmembrane activation are discussed. A novel mechanism is proposed involving the reorganization of a receptor oligomer from a specific inhibited state into an uninhibited state. Future directions of research based on the work presented in this thesis are suggested.
by Thomas O. Cameron.
Ph.D.
40
Hellström, Martin. „Hyaluronan and the receptor CD 44 in the heart and vessels : a study in normal and pathological conditions /“. Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1128.
41
Bernhard, Oliver. „Proteomic investigation of the HIV receptors CD4 and DC-SIGN/CD209 membrane protein interactions“. Saarbrücken VDM Verlag Dr. Müller, 2004. http://d-nb.info/989278026/04.
42
Vong, Allen M. „Late Antigen Regulates the Differentiation of Cytotoxic CD4 T Cells in Influenza Infection“. eScholarship@UMMS, 2012. http://escholarship.umassmed.edu/gsbs_diss/933.
Annotation:
CD4 T cells differentiate into multiple effector subsets that mediate pathogen clearance. ThCTL are anti-viral effectors with MHC-II restricted cytotoxicity. The factors regulating ThCTL generation are unclear, in part due to a lack of a signature marker. I show here that in mice, NKG2C/E identifies ThCTL that develop in the lung during influenza A virus (IAV) infection. ThCTL phenotype indicates they are highly activated effectors with high levels of binding to P-selectin, T-bet, IFNγ production, and degranulation. ThCTL express increased levels of granzymes and perforin and lower levels of genes associated with memory and recirculation compared to non-ThCTL lung effectors. ThCTL are also restricted to the site of infection, the lung in IAV and systemically in LCMV. ThCTL require Blimp-1 for their differentiation, suggesting a unique effector CD4 population. As ThCTL are highly activated, they also require antigen signaling post priming during IAV infection. Late antigen was necessary and sufficient for the differentiation of ThCTL. In the context of late antigen encounter, ThCTL surprisingly do not require CD80 and CD86 costimulation for their differentiation. Additionally ThCTL do not require late IL-2 for their differentiation and instead require late IL-15 signals for their efficient generation. Thus these data suggest ThCTL are marked by the expression of NKG2C/E and represent a unique CD4 effector population specialized for cytotoxicity.
43
Vong, Allen M. „Late Antigen Regulates the Differentiation of Cytotoxic CD4 T Cells in Influenza Infection“. eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/933.
Annotation:
CD4 T cells differentiate into multiple effector subsets that mediate pathogen clearance. ThCTL are anti-viral effectors with MHC-II restricted cytotoxicity. The factors regulating ThCTL generation are unclear, in part due to a lack of a signature marker. I show here that in mice, NKG2C/E identifies ThCTL that develop in the lung during influenza A virus (IAV) infection. ThCTL phenotype indicates they are highly activated effectors with high levels of binding to P-selectin, T-bet, IFNγ production, and degranulation. ThCTL express increased levels of granzymes and perforin and lower levels of genes associated with memory and recirculation compared to non-ThCTL lung effectors. ThCTL are also restricted to the site of infection, the lung in IAV and systemically in LCMV. ThCTL require Blimp-1 for their differentiation, suggesting a unique effector CD4 population. As ThCTL are highly activated, they also require antigen signaling post priming during IAV infection. Late antigen was necessary and sufficient for the differentiation of ThCTL. In the context of late antigen encounter, ThCTL surprisingly do not require CD80 and CD86 costimulation for their differentiation. Additionally ThCTL do not require late IL-2 for their differentiation and instead require late IL-15 signals for their efficient generation. Thus these data suggest ThCTL are marked by the expression of NKG2C/E and represent a unique CD4 effector population specialized for cytotoxicity.
44
Shim, Ho-Ki. „Mechanisms of antigen processing and presentation of CD4 T cell epitopes from the V antigen of Yersinia pestis“. Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405355.
45
Jones, Sian Helen. „Analysis of the mouse CD4 T cell repertoire by high efficiency cloning“. Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287160.
46
Stillger, Simone. „Aberrante CD45-Expression bei chronischer lymphatischer Leukämie ein möglicher Ansatzpunkt für eine neue Therapie?“ Göttingen Sierke, 2007. http://d-nb.info/987489542/04.
47
Prill, Thomas. „Transiente genetische Markierung CD34-positiver hämatopoetischer Stammzellen für die in vivo Applikation - Implikationen für eine therapeutische Myokardregeneration“. [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-56186.
48
Bonnard, Madeleine. „A novel role for CD4 in antigen-mediated T-cell activation /“. Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68156.
Annotation:
A number of T-cell membrane molecules influence the outcome of antigen recognition by TCR/CD3 complex. CD4, by virtue of its non-covalent association with the protein tyrosine kinase lck has the capacity to enhance TCR$ alpha beta$ signalling. The extracellular domain of CD4 interacts with monomorphic determinants of Major Histocompatibility complex class-II molecules such that antigen presented in association with MHC class-II to CD4$ sp+$ T-cells results in the coaggregation of CD4 and TCR/CD3, thus juxtaposing lck and the antigen-receptor complex. Anti-CD4 antibodies abrogate both antigen and anti-TCR-induced T-cell activation. Studies using antigen specific T-cell clones that express either no CD4, wild type CD4 or mutated CD4 that cannot associate with lck (Db CYS) indicate that CD4 sequesters the majority of cellular lck and when not coaggregated with TCR/CD3, prevents the generation of prerequisite signals.Results presented in this thesis indicate that while CD4-associated lck is providing prerequisite signals for TCR/CD3 signalling, the contribution of CD4 must be more than simply providing a shuttle for lck. Specifically, anti-CD4 inhibits the antigen response of Db CYS CD4-expressing clones. This result cannot be accounted for either by CD4 sequestration of lck, or reduction of avidity of the interaction between the T-cell and the antigen presenting cell, since CD4$ sp-$ variants exhibit an antigen response comparable to that of CD4$ sp+$ variants. Rather, they suggest a novel role for the ectodomain of CD4 in antigen-induced T-cell activation.
49
Han, Sushan. „Antigen-specific CD4+T cells in Anaplasma marginale infection of calves“. Pullman, Wash. : Washington State University, 2010. http://www.dissertations.wsu.edu/Dissertations/Spring2010/S_Han_121509.pdf.
50
Karhukorpi, J. (Jari). „The search for links between immunogenetic factors and recurrent miscarriage“. Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514277449.
Annotation:
Abstract
Successful pregnancy is characterized by a shift toward Th2 type immune response and suppression of adaptive immune responses to ensure acceptance of the semi-allogenic fetal graft. Also the innate immune system plays a major role during pregnancy. Recurrent miscarriage is defined as three or more consecutive pregnancy losses. About 1% of all women will suffer recurrent miscarriage. The causes of recurrent miscarriage remain unexplained in half (50%) of the cases. Susceptibility to recurrent miscarriage is probably mediated by Th1 type immune response with pronounced expression and secretion of pro-inflammatory cytokines (e.g. TNFα and IFNγ) paralleled with decreased production of anti-inflammatory cytokines (e.g. IL-10). Factors that regulate immune response during pregnancy include hormonal factors (e.g. hCG and progesterone). Immunogenetic factors also contribute to this regulation. Several functionally important polymorphisms in various immunomodulatory genes have been identified during recent years. Some of these polymorphisms may be important in regulating the Th1/Th2 balance during pregnancy. Putative immune dysregulation caused by these polymorphisms has been researched intensively. Conflicting results have been published about associations between several of these polymorphisms and recurrent miscarriage.
In this study, HLA-G (exon 2 and 3), IL-10 (-1082A/G), IL-1RA (intron 2 VNTR) and CD14 (-159C/T) polymorphisms were studied in 38 Finnish women with RM. All of these polymorphisms have been associated with altered gene expression. Distribution of HLA-G*I, II, III and IV were 0.577, 0.375, 0 and 0.048 respectively in the studied Finnish population. According to the present classification the G*I allele group mostly consists of the allele 010101, while G*II covers the combination of 010102, 010401 and 0105N, as well as some other rare alleles. There were no associations between recurrent miscarriage and the HLA-G, IL-10 and CD14 polymorphisms. However, in IL-1RA polymorphism, the rare IL1RN*3 allele was increased in women with recurrent miscarriage. It is not known, if this particular allele is associated with differences in IL-1RA or IL-1 production.
Although the study population was small, it may be supposed that quantitative differences in the production of single immunomodulatory molecules due to normal genetic variation may not be grossly harmful to the fetal allograft. This indicates the robustness and flexibility of the reproduction system. For survival, it is essential that minor variations are tolerated. Thus, large-scale studies focusing on the effect of a pro-inflammatory genetic profile based on the presence of several pro/anti-inflammatory genetic markers are needed to discover if immunogenetic factors predispose women to recurrent miscarriage.