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.
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
Joseph W
JW
Carl
Jin-Qing
JQ
Liu
Pramod S
PS
Joshi
Hani Y
HY
El-Omrani
Lijie
L
Yin
Xincheng
X
Zheng
Caroline C
CC
Whitacre
Yang
Y
Liu
Xue-Feng
XF
Bai
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