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 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.
Gao
Jian-Xin
JX
Department of Pathology and Comprehensive Cancer Center, Division of Cancer Immunology, Ohio State University Medical Center, Columbus, OH 43210, USA.
Zhang
Huiming
H
Bai
Xue-Feng
XF
Wen
Jing
J
Zheng
Xincheng
X
Liu
Jinqing
J
Zheng
Pan
P
Liu
Yang
Y
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007422:Intestines / Q000276:immunology; D008168:Lung / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; C076546:tumor rejection antigen P815A, mouse