Speiser D E, Zinkernagel R M
Institute of Pathology, University Hospital, Zürich, Switzerland.
Thymus. 1990 Nov-Dec;16(3-4):187-93.
Susceptibility of mice to intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) depends on the LCMV isolate and host genes. We have previously shown that major histocompatibility complex (MHC) class I genes regulate susceptibility to lethal disease due to infection with the LCMV-docile isolate derived from the LCMV-UBC strain. The Dq allele conferred dominant susceptibility whereas other H-2D region alleles tested (Dd, Dk, Db and Ds) conferred resistance. Susceptibility linked to Dq correlated strongly with early and potent LCMV-specific cytotoxic T cell (CTL) activation responsible for the CTL mediated immunopathological disease. To assess the extent to which thymic MHC products control lethal LCM, two studies were performed. First, (H-2Dk x H-2Dq)F1 bone marrow stem cells were used to reconstitute lethally irradiated recipients of each parental type. Reconstituted H-2Dk hosts were found to be resistant whereas H-2Dq hosts were susceptible to lethal LCM after i.c. infection, indicating that the phenotype of disease susceptibility was determined by the host. Second, we investigated the role of the thymus in the determination of resistance or susceptibility to LCM. Previously thymectomized (H-2Dk x H-2Dq)F1 mice received a thymus graft from either H-2Dk or H-2Dq fetal mice. After differentiation of F1 lymphoid precursor cells in the implanted thymus, susceptibility to lethal LCM was assessed. F1 recipient mice carrying a thymus expressing Dk were resistant whereas those carrying a thymus expressing Dq were susceptible. Therefore, as an extension of various previous studies on T cell immune responses, our results document directly that disease susceptibility to lethal LCM is controlled by MHC class I molecules of the thymus.
小鼠对淋巴细胞性脉络丛脑膜炎病毒（LCMV）脑内（i.c.）感染的易感性取决于LCMV分离株和宿主基因。我们之前已经表明，主要组织相容性复合体（MHC）I类基因调节因感染源自LCMV-UBC株的LCMV-温顺分离株而导致的致死性疾病的易感性。Dq等位基因赋予显性易感性，而测试的其他H-2D区域等位基因（Dd、Dk、Db和Ds）赋予抗性。与Dq相关的易感性与早期且强效的LCMV特异性细胞毒性T细胞（CTL）激活密切相关，这种激活导致CTL介导的免疫病理疾病。为了评估胸腺MHC产物控制致死性LCM的程度，进行了两项研究。首先，使用（H-2Dk×H-2Dq）F1骨髓干细胞重建每种亲本类型的致死性照射受体。发现重建的H-2Dk宿主具有抗性，而H-2Dq宿主在脑内感染后对致死性LCM易感，这表明疾病易感性表型由宿主决定。其次，我们研究了胸腺在决定对LCM的抗性或易感性中的作用。先前接受胸腺切除的（H-2Dk×H-2Dq）F1小鼠接受来自H-2Dk或H-2Dq胎鼠的胸腺移植。在植入的胸腺中F1淋巴前体细胞分化后，评估对致死性LCM的易感性。携带表达Dk的胸腺的F1受体小鼠具有抗性，而携带表达Dq的胸腺的小鼠易感。因此，作为先前关于T细胞免疫反应的各种研究的延伸，我们的结果直接证明对致死性LCM的疾病易感性由胸腺的MHC I类分子控制。
