Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway
Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway
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DOI：
10.4049/jimmunol.181.1.320
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Bai, Xue-Feng
中科院分区：
文献类型：
--
作者：
Carl, Joseph W., Jr.;Liu, Jin-Qing;Bai, Xue-Feng
尽管胸腺中存在负选择，但当免疫调节出现问题时，大量自身反应性 T 细胞仍然逃逸到外周并导致自身免疫性疾病。目前尚不清楚这些 T 细胞如何逃脱克隆删除。在这项研究中，我们报告 CD24 缺陷导致通常逃避阴性选择的自身反应性 T 细胞缺失。仅恢复 T 细胞上的 CD24 表达并不能阻止自身反应性 T 细胞的缺失；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 细胞缺失是必要的。 CD24 缺陷消除了具有针对致病性自身抗原的 TCR 特异性的转基因小鼠中实验性自身免疫性脑脊髓炎的发展。 CD24 在负选择中的作用为其控制小鼠和人类自身免疫性疾病的遗传易感性提供了新的解释。
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.