Department of Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Immunol. 2010 Aug 15;185(4):2089-98. doi: 10.4049/jimmunol.1000818. Epub 2010 Jul 12.
CD8 T cells can acquire cytokine-secreting phenotypes paralleling cytokine production from Th cells. IL-17-secreting CD8 T cells, termed Tc17 cells, were shown to promote inflammation and mediate immunity to influenza. However, most reports observed a lack of cytotoxic activity by Tc17 cells. In this study, we explored the anti-viral activity of Tc17 cells using a vaccinia virus (VV) infection model. Tc17 cells expanded during VV infection, and TCR transgenic Tc17 cells were capable of clearing recombinant VV infection. In vivo, adoptively transferred Tc17 cells lost the IL-17-secreting phenotype, even in the absence of stimulation, but they did not acquire IFN-gamma-secreting potential unless stimulated with a virus-encoded Ag. However, examination of cells following infection demonstrated that these cells acquired cytotoxic potential in vivo, even in the absence of IFN-gamma. Cytotoxic potential correlated with Fasl expression, and the cytotoxic activity of postinfection Tc17 cells was partially blocked by the addition of anti-FasL. Thus, Tc17 cells mediate VV clearance through expression of specific molecules associated with cytotoxicity but independent of an acquired Tc1 phenotype.
CD8 T 细胞可以获得与 Th 细胞产生细胞因子相似的细胞因子分泌表型。已证明分泌白介素 17 的 CD8 T 细胞（称为 Tc17 细胞）可促进炎症并介导对流感的免疫。然而，大多数报道观察到 Tc17 细胞缺乏细胞毒性活性。在这项研究中，我们使用牛痘病毒（VV）感染模型来探索 Tc17 细胞的抗病毒活性。在 VV 感染期间扩增了 Tc17 细胞，并且 TCR 转基因 Tc17 细胞能够清除重组 VV 感染。在体内，过继转移的 Tc17 细胞失去了分泌白介素 17 的表型，即使在没有刺激的情况下也是如此，但除非用病毒编码的 Ag 刺激，否则它们不会获得分泌 IFN-γ的潜能。然而，对感染后细胞的检查表明，这些细胞在体内获得了细胞毒性潜能，即使在没有 IFN-γ的情况下也是如此。细胞毒性潜能与 Fasl 表达相关，并且添加抗 Fasl 部分阻断了感染后 Tc17 细胞的细胞毒性活性。因此，Tc17 细胞通过表达与细胞毒性相关的特定分子而不是获得性 Tc1 表型来介导 VV 清除。
