دورية أكاديمية
CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire.
| العنوان: | CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire. |
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| المؤلفون: | Verhagen, J., Genolet, R., Britton, G.J., Stevenson, B.J., Sabatos-Peyton, C.A., Dyson, J., Luescher, I.F., Wraith, D.C. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 3, pp. E221-E230 |
| سنة النشر: | 2013 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Amino Acid Sequence, Animals, Antigenic Variation, CTLA-4 Antigen/deficiency, CTLA-4 Antigen/genetics, Cell Differentiation, Complementarity Determining Regions, Cytokines/biosynthesis, Dendritic Cells/cytology, Dendritic Cells/immunology, Encephalomyelitis, Autoimmune, Experimental/genetics, Experimental/immunology, Female, Gene Rearrangement, T-Lymphocyte, Male, Mice, Knockout, Transgenic, Molecular Sequence Data, Receptors, Antigen, T-Cell, alpha-beta/genetics, Self Tolerance, T-Lymphocytes/cytology, T-Lymphocytes/immunology, T-Lymphocytes |
| الوصف: | Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease. Tolerance to self-antigens is achieved through thymic deletion of highly autoreactive conventional T (Tconv) cells and generation of FoxP3(+) regulatory T (Treg) cells. The main costimulatory molecule, CD28, augments the negative selection of Tconv cells and promotes the generation of FoxP3(+) Treg cells. The role of its antagonistic homolog CTLA-4, however, remains a topic of debate. To address this topic, we investigated the thymic development of T cells in the presence and absence of CTLA-4 in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1-9. We reveal that CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells generated and broadens the repertoire of peripheral Tconv cells. T-cell repertoire alteration after deletion of CTLA-4 results from changes in TCR Vα and Jα segment selection as well as CDR3α composition in Tconv and Treg cells. CTLA-4, therefore, regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0027-8424 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/23267099; info:eu-repo/semantics/altIdentifier/eissn/1091-6490; https://serval.unil.ch/notice/serval:BIB_C32A40C6995CTest; urn:issn:0027-8424 |
| DOI: | 10.1073/pnas.1208573110 |
| الإتاحة: | https://doi.org/10.1073/pnas.1208573110Test https://serval.unil.ch/notice/serval:BIB_C32A40C6995CTest |
| رقم الانضمام: | edsbas.372FABF7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00278424 |
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| DOI: | 10.1073/pnas.1208573110 |