Virus-specific and bystander CD8 T cells recruited during virus-induced encephalomyelitis
Virus-specific and bystander CD8 T cells recruited during virus-induced encephalomyelitis
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DOI：
10.1128/jvi.79.8.4700-4708.2005
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Bergmann, CC
中科院分区：
文献类型：
--
作者：
Chen, AM;Khanna, N;Bergmann, CC
嗜神经性冠状病毒诱导的脑炎用于评估外周旁观者记忆CD8（+）T细胞的募集、功能激活和保留。首先用表达非交叉反应性人免疫缺陷病毒（HIV）表位（命名为p18）的重组牛痘病毒感染小鼠。在建立内源性p18特异性记忆性CD8（+）T细胞群后，用冠状病毒攻击小鼠，以直接比较主要冠状病毒特异性和旁观者记忆性细胞群进入中枢神经系统（CNS）的募集、寿命和激活特征。HIV特异性记忆性CD8（+）T细胞作为先天免疫应答的组成部分被早期募集到CNS中，先于对主要冠状病毒表位特异性的CD8（+）T细胞，命名为pN。虽然pN特异性T细胞数量逐渐超过旁观者p18特异性CD8（+）T细胞数量，但两个群体在CNS内同时达到峰值。然而，冠状病毒特异性CD8（+）T细胞优先保留。相比之下，在CNS病毒复制得到控制后，旁观者CD8（+）T细胞数量下降至背景数量。此外，与高度活化的pN特异性CD8（+）T细胞相反，募集到炎症部位的旁观者p18特异性CD8（+）T细胞保持非活化记忆表型，并且不表达离体细胞溶解活性。因此，对宿主CD8（+）T细胞对无关感染的反应的分析表明，旁观者记忆CD8（+）T细胞在病毒诱导的脑炎期间可以包含显著比例的CNS炎性细胞。然而，短暂的中枢神经系统滞留和缺乏激活表明，记忆旁观者CD8（+）T细胞可能不会明显有助于在抗原识别的情况下的病理。
Neurotropic coronavirus-induced encephalitis was used to evaluate recruitment, functional activation, and retention of peripheral bystander memory CD8(+) T cells. Mice were first infected with recombinant vaccinia virus expressing a non-cross-reactive human immunodeficiency virus (HIV) epitope, designated p18. Following establishment of an endogenous p18-specific memory CD8(+) T-cell population, mice were challenged with coronavirus to directly compare recruitment, longevity, and activation characteristics of both primary coronavirus-specific and bystander memory populations trafficking into the central nervous system (CNS). HIV-specific memory CD8(+) T cells were recruited early into the CNS as components of the innate immune response, preceding CD8(+) T cells specific for the dominant coronavirus epitope, designated pN. Although pN-specific T-cell numbers gradually exceeded bystander p18-specific CD8(+) T-cell numbers, both populations peaked concurrently within the CNS. Nevertheless, coronavirus-specific CD8(+) T cells were preferentially retained. By contrast, bystander CD8(+) T-cell numbers declined to background numbers following control of CNS virus replication. Furthermore, in contrast to highly activated pN-specific CD8(+) T cells, bystander p18-specific CD8(+) T cells recruited to the site of inflammation maintained a nonactivated memory phenotype and did not express ex vivo cytolytic activity. Therefore, analysis of host CD8(+) T-cell responses to unrelated infections demonstrates that bystander memory CD8(+) T cells can comprise a significant proportion of CNS inflammatory cells during virus-induced encephalitis. However, transient CNS retention and the absence of activation suggest that memory bystander CD8(+) T cells may not overtly contribute to pathology in the absence of antigen recognition.