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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15 April 2002
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April 08 2002
Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
Jian-Xin Gao,
Jian-Xin Gao
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Huiming Zhang,
Huiming Zhang
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Xue-Feng Bai,
Xue-Feng Bai
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Jing Wen,
Jing Wen
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Xincheng Zheng,
Xincheng Zheng
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Jinqing Liu,
Jinqing Liu
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Pan Zheng,
Pan Zheng
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Yang Liu
Yang Liu
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
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Jian-Xin Gao
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Huiming Zhang
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Xue-Feng Bai
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Jing Wen
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Xincheng Zheng
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Jinqing Liu
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Pan Zheng
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Yang Liu
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210
Address correspondence to Yang Liu, Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210. Phone: 614-292-3054; Fax: 614-688-8152; E-mail: [email protected]
*
Abbreviations used in this paper: CTLA-4, cytotoxic T lymphocyte–associated molecule 4; H&E, hematoxylin and eosin; NOD, nonobese diabetic; P1CTL, H-2Ld–restricted, P1A-specific TCR; RAG-1, recombinase activating gene 1; VSAg, viral superantigen.
Received:
November 20 2001
Revision Received:
February 05 2002
Accepted:
February 22 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (8): 959–971.
Article history
Received:
November 20 2001
Revision Received:
February 05 2002
Accepted:
February 22 2002
Citation
Jian-Xin Gao, Huiming Zhang, Xue-Feng Bai, Jing Wen, Xincheng Zheng, Jinqing Liu, Pan Zheng, Yang Liu; Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells . J Exp Med 15 April 2002; 195 (8): 959–971. doi: https://doi.org/10.1084/jem.20011948
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