CD4+ CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions
CD4+ CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions
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DOI：
10.4049/jimmunol.172.7.4123
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Rouse, BT
中科院分区：
文献类型：
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作者：
Suvas, S;Azkur, AK;Rouse, BT
CD4(+)CD25（+）调节性T细胞（T-reg）可以抑制多种自身免疫性和炎症性疾病，但它们在调节病毒诱导的免疫病理中的作用尚不清楚。我们评估了T-reg在病毒性免疫病理病变间质角膜炎中的作用。这种人类失明的常见原因是由于角膜基质中T细胞介导的对HSV的免疫炎症反应。结果表明，如果小鼠在感染前耗尽T-reg，则病变明显更严重。T-reg也被证明可以调节受感染SCID受体中致病性CD4(+) T细胞过继性转移引起的病变表达。T-reg控制间质角膜炎的机制涉及抑制抗病毒免疫和T细胞向病变部位迁移所需分子的表达受损。有趣的是，从非衰竭小鼠眼部病变中分离的T-reg显示出涉及IL-10的体外抑制作用，但在已建立的病变中不是很有效。我们的研究结果破译了T-reg在病毒诱导的免疫病理中的体内作用，并暗示操纵调节性细胞功能代表了控制病毒诱导的免疫炎症疾病的有用方法。
CD4(+)CD25(+) regulatory T cells (T-reg) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T-reg in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of T-reg before infection. The T-reg was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4(+) T cells in infected SCID recipients. The mechanism of T-reg control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, T-reg isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of T-reg, in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.