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Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes
The development of a normal T cell repertoire in the thymus is dependent on the interplay between signals mediating cell survival (positive selection) and cell death (negative selection or death by neglect). Although the CD28 costimulatory molecule has been implicated in this process, it has been di...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212496/ https://www.ncbi.nlm.nih.gov/pubmed/9763603 |
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author | Cilio, Corrado M. Daws, Michael R. Malashicheva, Anna Sentman, Charles L. Holmberg, Dan |
author_facet | Cilio, Corrado M. Daws, Michael R. Malashicheva, Anna Sentman, Charles L. Holmberg, Dan |
author_sort | Cilio, Corrado M. |
collection | PubMed |
description | The development of a normal T cell repertoire in the thymus is dependent on the interplay between signals mediating cell survival (positive selection) and cell death (negative selection or death by neglect). Although the CD28 costimulatory molecule has been implicated in this process, it has been difficult to establish a role for the other major costimulatory molecule, cytotoxic T lymphocyte antigen (CTLA)-4. Here we report that in vivo stimulation through the T cell receptor (TCR)–CD3 complex induces expression of CTLA-4 in thymocytes and leads to the association of CTLA-4 with the SH2 domain–containing phosphatase (SHP)-2 tyrosine phosphatase. Moreover, intrathymic CTLA-4 blockade dramatically inhibits anti-CD3–mediated depletion of CD4(+)CD8(+) double positive immature thymocytes. Similarly, anti-CD3–mediated depletion of CD4(+)CD8(+) double positive cells in fetal thymic organ cultures could also be inhibited by anti–CTLA-4 antibodies. Thus, our data provide evidence for a role of CTLA-4 in thymic selection and suggest a novel mechanism contributing to the regulation of TCR-mediated selection of T cell repertoires. |
format | Text |
id | pubmed-2212496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22124962008-04-16 Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes Cilio, Corrado M. Daws, Michael R. Malashicheva, Anna Sentman, Charles L. Holmberg, Dan J Exp Med Articles The development of a normal T cell repertoire in the thymus is dependent on the interplay between signals mediating cell survival (positive selection) and cell death (negative selection or death by neglect). Although the CD28 costimulatory molecule has been implicated in this process, it has been difficult to establish a role for the other major costimulatory molecule, cytotoxic T lymphocyte antigen (CTLA)-4. Here we report that in vivo stimulation through the T cell receptor (TCR)–CD3 complex induces expression of CTLA-4 in thymocytes and leads to the association of CTLA-4 with the SH2 domain–containing phosphatase (SHP)-2 tyrosine phosphatase. Moreover, intrathymic CTLA-4 blockade dramatically inhibits anti-CD3–mediated depletion of CD4(+)CD8(+) double positive immature thymocytes. Similarly, anti-CD3–mediated depletion of CD4(+)CD8(+) double positive cells in fetal thymic organ cultures could also be inhibited by anti–CTLA-4 antibodies. Thus, our data provide evidence for a role of CTLA-4 in thymic selection and suggest a novel mechanism contributing to the regulation of TCR-mediated selection of T cell repertoires. The Rockefeller University Press 1998-10-05 /pmc/articles/PMC2212496/ /pubmed/9763603 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Cilio, Corrado M. Daws, Michael R. Malashicheva, Anna Sentman, Charles L. Holmberg, Dan Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title | Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title_full | Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title_fullStr | Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title_full_unstemmed | Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title_short | Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of Thymocytes |
title_sort | cytotoxic t lymphocyte antigen 4 is induced in the thymus upon in vivo activation and its blockade prevents anti-cd3–mediated depletion of thymocytes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212496/ https://www.ncbi.nlm.nih.gov/pubmed/9763603 |
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