Welsh R M, Lin M Y, Lohman B L, Varga S M, Zarozinski C C, Selin L K
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Immunol Rev. 1997 Oct;159:79-93. doi: 10.1111/j.1600-065x.1997.tb01008.x.
Both alpha beta and gamma delta T-cell populations and natural killer (NK) cells include cytotoxic, interferon (IFN)-gamma-producing lymphocytes that actively respond to viral infections. We show here that all three populations can provide "natural resistance" to viruses very early in infection and describe how the T-cell populations are modulated to provide this function. gamma delta T cells were shown to play a role in controlling vaccinia virus (VV) infections, as VV grew to much higher titers in gamma delta T-cell knockout mice than in normal mice 3-4 days post-infection. Our studies of the alpha beta T-cell responses to viruses revealed an interactive network of T cells that is modulated substantially during systemic infections. There is an induction phase associated with a massive virus-specific CD8 T-cell response, an apoptosis phase during which the T cells become sensitized to activation-induced cell death (AICD), a silencing phase, during which the T-cell number and activation state is reduced, and, finally, a memory phase associated with the very stable preservation of virus-specific memory cytotoxic T-lymphocyte precursors (pCTL). Infection of mice immune to one virus with a heterologous virus leads to a selective expansion of memory CTL cross-reacting between the two viruses, but, after homeostasis is again established, there is a quantitative reduction and qualitative alteration of memory to the first virus. Our results suggest that memory alpha beta T cells cross-reactive between heterologous viruses mediate both immunopathology and protective immunity at early stages of the second virus infection. Thus, memory alpha beta T cells can, like gamma delta T cells and NK cells, provide natural immunity to viral infections.
αβ和γδT细胞群体以及自然杀伤（NK）细胞均包含具有细胞毒性、能产生干扰素（IFN）-γ的淋巴细胞，这些细胞可积极应对病毒感染。我们在此表明，这三种细胞群体在感染早期均可对病毒提供“天然抗性”，并描述了T细胞群体如何被调节以发挥此功能。γδT细胞在控制痘苗病毒（VV）感染中发挥作用，因为在感染后3 - 4天，VV在γδT细胞敲除小鼠中的滴度比正常小鼠高得多。我们对αβT细胞对病毒反应的研究揭示了一个T细胞相互作用网络，该网络在全身感染期间会发生显著调节。存在一个与大量病毒特异性CD8 T细胞反应相关的诱导期、一个T细胞对激活诱导的细胞死亡（AICD）敏感的凋亡期、一个T细胞数量和激活状态降低的沉默期，最后是一个与病毒特异性记忆细胞毒性T淋巴细胞前体（pCTL）非常稳定保存相关的记忆期。用异源病毒感染对一种病毒免疫的小鼠会导致两种病毒之间交叉反应的记忆CTL选择性扩增，但在再次建立稳态后，对第一种病毒的记忆会出现数量减少和质量改变。我们的结果表明，在异源病毒之间交叉反应的记忆αβT细胞在第二种病毒感染的早期阶段介导免疫病理学和保护性免疫。因此，记忆αβT细胞与γδT细胞和NK细胞一样，可为病毒感染提供天然免疫。
