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实验性变应性脑脊髓炎的超抗原调节:无反应性的激活决定结果。

Superantigen modulation of experimental allergic encephalomyelitis: activation of anergy determines outcome.

作者信息

Racke M K, Quigley L, Cannella B, Raine C S, McFarlin D E, Scott D E

机构信息

Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Immunol. 1994 Feb 15;152(4):2051-9.

PMID:8120406
Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced by the adoptive transfer of CD4, myelin basic protein (MBP)-specific T cells. Superantigens activate T cells expressing appropriate TCR V genes. In this study, MBP-specific T cells activated in vitro with a superantigen, staphylococcal enterotoxin B (SEB), could adoptively transfer a severe form of EAE in (PLxSJL)F1 mice, but did not transfer disease in PL/J or SJL/J mice. SEB treatment of donor mice anergized MBP-specific T cells using V beta 8 in (PLxSJL)F1 mice, because subsequent in vitro activation with SEB resulted in a marked decrease in proliferation to SEB and inability to transfer EAE. However, donor cells from (PLxSJL)F1 mice immunized with MBP/CFA that had been exposed to SEB in vivo before MBP stimulation in vitro still produced EAE in recipient mice. To confirm that non-V beta 8 T cells could transfer disease, donor mice were treated with antibody that eliminated V beta 8 T cells; MBP-activated T cells from these mice could still transfer EAE. Finally, EAE induced by SEB-activated T cells was substantially reduced in mice receiving anti-V beta 8 therapy in vivo. The ability of superantigens to activate encephalitogenic T cells may have relevance to human diseases such as multiple sclerosis.

摘要

实验性变应性脑脊髓炎(EAE)是一种自身免疫性疾病,可通过过继转移CD4、髓鞘碱性蛋白(MBP)特异性T细胞诱导产生。超抗原可激活表达适当TCR V基因的T细胞。在本研究中,用超抗原葡萄球菌肠毒素B(SEB)体外激活的MBP特异性T细胞,可在(PLxSJL)F1小鼠中过继转移严重形式的EAE,但在PL/J或SJL/J小鼠中不能转移疾病。在(PLxSJL)F1小鼠中,SEB处理供体小鼠可使利用Vβ8的MBP特异性T细胞失能,因为随后用SEB进行体外激活会导致对SEB的增殖显著降低且无法转移EAE。然而,来自(PLxSJL)F1小鼠的供体细胞,在体外MBP刺激前已在体内接触过SEB的情况下,用MBP/完全弗氏佐剂免疫后,仍能在受体小鼠中产生EAE。为证实非Vβ8 T细胞可转移疾病,用消除Vβ8 T细胞的抗体处理供体小鼠;来自这些小鼠的MBP激活的T细胞仍可转移EAE。最后,在体内接受抗Vβ8治疗的小鼠中,由SEB激活的T细胞诱导的EAE显著减少。超抗原激活致脑炎性T细胞的能力可能与诸如多发性硬化症等人类疾病相关。

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