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Autoreactive T Cells Escape Clonal Deletion in the Thymus by a CD24-Dependent Pathway¹

Joseph W. Carl, Jr.^*, Jin-Qing Liu^*, Pramod S. Joshi^*, Hani Y. El-Omrani^*, Lijie Yin, Xincheng Zheng, Caroline C. Whitacre, Yang Liu and Xue-Feng Bai^2,*

^* Department of Pathology and Comprehensive Cancer Center and Department of Virology, Immunology and Molecular Genetics, Ohio State University Medical Center, Columbus, OH 43210; Department of Surgery and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109; and OncoImmune, Inc., Columbus, OH 43212

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from National Multiple Sclerosis Society (RG 3638 to X.-F.B.) and Ohio Department of Development.

² Address correspondence and reprint requests to Dr. Xue-Feng Bai, Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210. E-mail address: Xue-Feng.Bai{at}osumc.edu

³ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; WT, wild type; TEC, thymic epithelial cells; DP, double positive; SP, single positive; DC, dendritic cell; VSAg, viral superantigen.

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