Kumaraguru U, Davis I A, Deshpande S, Tevethia S S, Rouse B T
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
J Immunol. 2001 Jan 15;166(2):1066-74. doi: 10.4049/jimmunol.166.2.1066.
Recent observations have indicated that viral persistence and tumor spreading could occur because of effector function-defective CD8(+) T cells. Although chronic exposure to Ag, lack of CD4 help, and epitope dominance are suggested to interfere with CTL differentiation, mechanisms underlying the defective effector function remain obscure. We demonstrate in this report that lymphotoxin alpha-deficient mice develop CD8(+) T cells at normal frequencies when infected with HSV or immunized with OVA Ag but show impaired cytotoxic and cytokine-mediated effector functions resulting in enhanced susceptibility to HSV-induced encephalitis. Although these cells display near normal levels of perforin and Fas ligand, they remain largely at a naive state as judged by high expression of CD62 ligand and failure to up-regulate activation or memory markers. In particular, these CD8(+) T cells revealed inadequate expression of the IL-12 receptor, thus establishing a link between CTL differentiation and LTalpha possibly through regulation of IL-12 receptor. Viruses and tumors could evade immunity by targeting the same pathway.
最近的观察结果表明，效应功能缺陷的CD8(+) T细胞可能导致病毒持续存在和肿瘤扩散。虽然长期暴露于抗原、缺乏CD4辅助以及表位优势被认为会干扰CTL分化，但效应功能缺陷的潜在机制仍不清楚。我们在本报告中证明，淋巴毒素α缺陷小鼠在感染HSV或用OVA抗原免疫时，能以正常频率产生CD8(+) T细胞，但显示出细胞毒性和细胞因子介导的效应功能受损，导致对HSV诱导的脑炎易感性增加。虽然这些细胞的穿孔素和Fas配体水平接近正常，但根据CD62配体的高表达以及未能上调激活或记忆标志物判断，它们在很大程度上仍处于幼稚状态。特别是，这些CD8(+) T细胞显示出IL-12受体表达不足，从而可能通过调节IL-12受体在CTL分化和LTα之间建立了联系。病毒和肿瘤可能通过靶向相同途径逃避免疫。
