Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway.
Despite negative selection in the thymus, significant numbers of autoreactive T cells still escape to the periphery and cause autoimmune diseases when immune regulation goes awry. It is largely unknown how these T cells escape clonal deletion. In this study, we report that CD24 deficiency caused deletion of autoreactive T cells that normally escape negative selection. Restoration of CD24 expression on T cells alone did not prevent autoreactive T cells from deletion; bone marrow chimera experiments suggest that CD24 on radio-resistant stromal cells is necessary for preventing deletion of autoreactive T cells. CD24 deficiency abrogated the development of experimental autoimmune encephalomyelitis in transgenic mice with a TCR specific for a pathogenic autoantigen. The role of CD24 in negative selection provides a novel explanation for its control of genetic susceptibility to autoimmune diseases in mice and humans.
Carl
Joseph W
JW
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
Liu
Jin-Qing
JQ
Joshi
Pramod S
PS
El-Omrani
Hani Y
HY
Yin
Lijie
L
Zheng
Xincheng
X
Whitacre
Caroline C
CC
Liu
Yang
Y
Bai
Xue-Feng
XF
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D051927:CD24 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype; D017154:Stromal Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D051927:CD24 Antigen; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein