Carl Joseph W, Liu Jin-Qing, Joshi Pramod S, El-Omrani Hani Y, Yin Lijie, Zheng Xincheng, Whitacre Caroline C, Liu Yang, Bai Xue-Feng
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
J Immunol. 2008 Jul 1;181(1):320-8. doi: 10.4049/jimmunol.181.1.320.
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.
尽管在胸腺中存在阴性选择，但当免疫调节出现紊乱时，仍有大量自身反应性T细胞逃避免疫清除并引发自身免疫性疾病。目前对于这些T细胞如何逃避免疫克隆清除尚不清楚。在本研究中，我们发现CD24缺陷导致通常逃避免疫阴性选择的自身反应性T细胞被清除。单独恢复T细胞上CD24的表达并不能阻止自身反应性T细胞被清除；骨髓嵌合体实验表明，抗辐射基质细胞上的CD24对于防止自身反应性T细胞被清除是必需的。在具有针对致病性自身抗原的TCR的转基因小鼠中，CD24缺陷消除了实验性自身免疫性脑脊髓炎的发生。CD24在阴性选择中的作用为其对小鼠和人类自身免疫性疾病遗传易感性的控制提供了新的解释。
