Perinatal blockade of B7-1 and B7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells

被引:52
作者
Gao, JX
Zhang, HM
Bai, XF
Wen, J
Zheng, XC
Liu, JQ
Zheng, P
Liu, Y
机构
[1] Ohio State Univ, Dept Pathol, Ctr Med, Div Canc Immunol, Columbus, OH 43210 USA
[2] Ohio State Univ, Ctr Comprehens Canc, Ctr Med, Div Canc Immunol, Columbus, OH 43210 USA
关键词
autoimmunity; clonal deletion; B7-1 and B7-2; CD28; CTLA-4;
D O I
10.1084/jem.20011948
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A number of in vitro studies have suggested that costimulatoty 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 subscantially 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.
引用
收藏
页码:959 / 971
页数:13
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