Lohman B L, Welsh R M
Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
J Virol. 1998 Oct;72(10):7815-21. doi: 10.1128/JVI.72.10.7815-7821.1998.
Acute viral infections often induce a transient period of immune deficiency in which the host's T cells fail to proliferate in response to T-cell mitogens and fail to make an antigen-specific memory recall response. This has been associated with the enhanced sensitivity of these highly activated T cells to undergo apoptosis, or activation-induced cell death (AICD), upon T-cell receptor ligation. Here we show that gamma interferon receptor-deficient (IFN-gamma R-/-) mice mount a T-cell response to lymphocytic choriomeningitis virus (LCMV) infection but fail to undergo the transient immune deficiency. Instead, their T cells were hyperproliferative and relatively, but not completely, resistant to AICD. The immune response returned to homeostasis, but with delayed kinetics, in parallel with delayed clearance of the virus. Wild-type mice receiving high doses of disseminating LCMV Clone 13 are known to undergo clonal exhaustion of their virus-specific cytotoxic T lymphocytes (CTL). To determine whether this process was mediated by AICD associated with IFN-gamma or with Fas-Fas ligand interactions, LCMV-specific precursor CTL frequencies were examined in LCMV Clone 13-infected IFN-gamma R-/- or lpr (Fas-deficient) mice. In both instances, viral persistence was established and CTL precursors were greatly eliminated. This finding indicates that clonal exhaustion of CTL does not require IFN-gamma or Fas, even though both molecules influence AICD and the transient immune deficiency seen in the LCMV infection.
急性病毒感染常常会引发一段短暂的免疫缺陷期，在此期间宿主的T细胞无法对T细胞有丝分裂原产生增殖反应，也无法做出抗原特异性的记忆性回忆反应。这与这些高度活化的T细胞在T细胞受体连接后对凋亡或活化诱导的细胞死亡（AICD）的敏感性增强有关。在此我们表明，γ干扰素受体缺陷（IFN-γR-/-）小鼠对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染会产生T细胞反应，但不会经历短暂的免疫缺陷。相反，它们的T细胞过度增殖，并且相对（但并非完全）抵抗AICD。免疫反应恢复到稳态，但动力学延迟，同时病毒清除也延迟。已知接受高剂量播散性LCMV克隆13的野生型小鼠会使其病毒特异性细胞毒性T淋巴细胞（CTL）发生克隆耗竭。为了确定这个过程是否由与IFN-γ相关的AICD或Fas-Fas配体相互作用介导，我们检测了LCMV克隆13感染的IFN-γR-/-或lpr（Fas缺陷）小鼠中LCMV特异性CTL前体细胞频率。在这两种情况下，都建立了病毒持续性感染，并且CTL前体细胞被大量清除。这一发现表明，CTL的克隆耗竭并不需要IFN-γ或Fas，尽管这两种分子都会影响AICD以及LCMV感染中出现的短暂免疫缺陷。
