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Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells

A number of in vitro studies have suggested that costimulatory molecules B7-1 and B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo studies have indicated that CD28 is involved in the clonal deletion of some T cells. However, the significance of B7-mediated clonal deletio...

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Autores principales: Gao, Jian-Xin, Zhang, Huiming, Bai, Xue-Feng, Wen, Jing, Zheng, Xincheng, Liu, Jinqing, Zheng, Pan, Liu, Yang
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193695/
https://www.ncbi.nlm.nih.gov/pubmed/11956287
http://dx.doi.org/10.1084/jem.20011948
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author Gao, Jian-Xin
Zhang, Huiming
Bai, Xue-Feng
Wen, Jing
Zheng, Xincheng
Liu, Jinqing
Zheng, Pan
Liu, Yang
author_facet Gao, Jian-Xin
Zhang, Huiming
Bai, Xue-Feng
Wen, Jing
Zheng, Xincheng
Liu, Jinqing
Zheng, Pan
Liu, Yang
author_sort Gao, Jian-Xin
collection PubMed
description A number of in vitro studies have suggested that costimulatory molecules B7-1 and B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo studies have indicated that CD28 is involved in the clonal deletion of some T cells. However, the significance of B7-mediated clonal deletion in preventing autoimmune diseases has not been studied systematically. Here we report that the perinatal blockade of B7-1 and B7-2 substantially inhibits the clonal deletion of T cells in the thymus and leads to an accumulation of T cells capable of inducing fatal multiorgan inflammation. These results reveal a critical role for costimulatory molecules B7-1 and B7-2 in deleting pathogenic autoreactive T cells in the thymus. The critical role of B7-1 and B7-2 in T cell clonal deletion may explain, at least in part, the paradoxical increase of autoimmune disease in mice deficient for this family of costimulatory molecules, such as cytotoxic T lymphocyte associated molecule 4, CD28, and B7-2. The strong pathogenicity of the self-reactive T cells supports a central hypothesis in immunology, which is that clonal deletion plays an important role in preventing autoimmune diseases.
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spelling pubmed-21936952008-04-14 Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells Gao, Jian-Xin Zhang, Huiming Bai, Xue-Feng Wen, Jing Zheng, Xincheng Liu, Jinqing Zheng, Pan Liu, Yang J Exp Med Article A number of in vitro studies have suggested that costimulatory molecules B7-1 and B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo studies have indicated that CD28 is involved in the clonal deletion of some T cells. However, the significance of B7-mediated clonal deletion in preventing autoimmune diseases has not been studied systematically. Here we report that the perinatal blockade of B7-1 and B7-2 substantially inhibits the clonal deletion of T cells in the thymus and leads to an accumulation of T cells capable of inducing fatal multiorgan inflammation. These results reveal a critical role for costimulatory molecules B7-1 and B7-2 in deleting pathogenic autoreactive T cells in the thymus. The critical role of B7-1 and B7-2 in T cell clonal deletion may explain, at least in part, the paradoxical increase of autoimmune disease in mice deficient for this family of costimulatory molecules, such as cytotoxic T lymphocyte associated molecule 4, CD28, and B7-2. The strong pathogenicity of the self-reactive T cells supports a central hypothesis in immunology, which is that clonal deletion plays an important role in preventing autoimmune diseases. The Rockefeller University Press 2002-04-15 /pmc/articles/PMC2193695/ /pubmed/11956287 http://dx.doi.org/10.1084/jem.20011948 Text en Copyright © 2002, The Rockefeller University Press 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 Article
Gao, Jian-Xin
Zhang, Huiming
Bai, Xue-Feng
Wen, Jing
Zheng, Xincheng
Liu, Jinqing
Zheng, Pan
Liu, Yang
Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title_full Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title_fullStr Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title_full_unstemmed Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title_short Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
title_sort perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193695/
https://www.ncbi.nlm.nih.gov/pubmed/11956287
http://dx.doi.org/10.1084/jem.20011948
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