Feedback regulation of murine autoimmunity via dominant anti-inflammatory effects of interferon γ

被引:23
作者
Minguela, Alfredo
Pastor, Silvia
Mi, Wentao
Richardson, James A.
Ward, E. Sally
机构
[1] Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA
[3] Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA
关键词
D O I
10.4049/jimmunol.178.1.134
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
There is a paucity of knowledge concerning the immunologic sequelae that culminate in overt autoimmunity. In the present study, we have analyzed the factors that lead to disease in the model of autoimmunity, murine experimental autoimmune encephalomyelitis (EAE). EAE in H-2(u) mice involves autoreactive CD4(+) T cells that are induced by immunization with the immunodominant N-terminal epitope of myelin basic protein. The affinity of this epitope for I-A(u) can be increased by substituting lysine at position 4 with tyrosine, and this can be used to increase the effective Ag dose. Paradoxically, high doses of Ag are poorly encephalitogenic. We have used quantitative analyses to study autoreactive CD4(+) T cell responses following immunization of mice with Ag doses that are at the extremes of encephalitogenicity. A dose of autoantigen that is poorly encephalitogenic results in T cell hyperresponsiveness, triggering an anti-inflammatory feedback loop in which IFN-gamma plays a pivotal role. Our studies define a regulatory mechanism that serves to limit overly robust T cell responses. This feedback regulation has broad relevance to understanding the factors that determine T cell responsiveness.
引用
收藏
页码:134 / 144
页数:11
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