Perforin-Deficient CD8+ T Cells Provide Immunity to Listeria monocytogenes by a Mechanism That Is Independent of CD95 and IFN-γ but Requires TNF-α
Perforin-Deficient CD8+ T Cells Provide Immunity to Listeria monocytogenes by a Mechanism That Is Independent of CD95 and IFN-γ but Requires TNF-α
复制标题
DOI：
10.4049/jimmunol.160.2.898
复制
发表时间：
1998-01
期刊：
影响因子：
--
通讯作者：
D. White;J. Harty
中科院分区：
文献类型：
--
作者：
D. White;J. Harty
CD 8 + T细胞是抗单核细胞增生李斯特菌免疫的有效介质，但它们提供抗单核细胞增生李斯特菌免疫的机制知之甚少。CD 8 + T细胞通过至少两种独立的途径在体外有效地裂解靶细胞。为了验证CD 8 + T细胞介导的抗L.由于单核细胞增多症依赖于穿孔素或CD 95（Fas，Apo-1），我们使用C57 B1/6（B6）和穿孔素缺陷（PO）小鼠产生对L.单核细胞生成素编码的嗜银蛋白溶血素O（LLO）。两种细胞系均特异性产生IFN-γ和TNF-α，并在体外介导靶细胞裂解。由PO衍生的CD 8 + T细胞系介导的细胞溶解相对于B6衍生的系延迟，并且被抗CD 95 Ab完全抑制。在体内，PO衍生的CD 8 + T细胞在B6宿主、CD 95缺陷型宿主和IFN-γ耗尽型宿主中提供特异性抗病毒免疫。然而，PO衍生的CD 8 + T细胞不能在TNF-α耗尽的宿主中提供抗病毒免疫。这些结果表明，来自PO小鼠的单个Ag特异性CD 8 + T细胞可以通过不依赖于CD 95或IFN-γ但需要TNF-α的机制介导抗病毒免疫。
CD8+ T cells are effective mediators of immunity against Listeria monocytogenes, but the mechanisms by which they provide antilisterial immunity are poorly understood. CD8+ T cells efficiently lyse target cells in vitro by at least two independent pathways. To test the hypothesis that CD8+ T cell-mediated immunity to L. monocytogenes is dependent on perforin or CD95 (Fas, Apo-1), we used C57Bl/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines specific for the L. monocytogenes-encoded Ag listeriolysin O (LLO). Both lines specifically produce IFN-γ and TNF-α, and mediate target cell lysis in vitro. Cytolysis mediated by the PO-derived CD8+ T cell line is delayed relative to the B6-derived line and is completely inhibited by anti-CD95 Abs. In vivo, PO-derived CD8+ T cells provide specific antilisterial immunity in B6 hosts, CD95-deficient hosts, and IFN-γ-depleted hosts. However, PO-derived CD8+ T cells fail to provide antilisterial immunity in hosts depleted of TNF-α. These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-γ, but requires TNF-α.