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白细胞介素-12可使抗性小鼠体内潜在的自身免疫疾病显现出来。

IL-12 unmasks latent autoimmune disease in resistant mice.

作者信息

Segal B M, Shevach E M

机构信息

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.

出版信息

J Exp Med. 1996 Aug 1;184(2):771-5. doi: 10.1084/jem.184.2.771.

Abstract

Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of the susceptible SJL (H-2s) and resistant B10.S (H-2s) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th 1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases.

摘要

近交系小鼠对实验性自身免疫性脑脊髓炎(EAE)的诱导表现出一系列易感性。我们比较了易感的SJL(H-2s)和抗性的B10.S(H-2s)品系的免疫反应,以确定除MHC背景之外控制对EAE抗性/易感性的其他因素。发现B10.S品系的抗性是由于产生IFNγ的Th1细胞生成中的抗原特异性缺陷所致。通过使髓鞘碱性蛋白(MBP)反应性T细胞暴露于IL-12,随后诱导将EAE转移至未接触过抗原的受体的能力,可以恢复IFNγ产生的这种缺陷。这些发现对IL-12和IL-12拮抗剂的治疗用途具有重要意义,并且可能解释自身免疫性疾病与传染病的复发/加重之间的关联。

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