Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system
Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system
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DOI：
10.1016/s0042-6822(03)00237-x
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发表时间：
2003-08-01
期刊：
影响因子：
3.7
通讯作者：
Lane, TE
中科院分区：
文献类型：
--
作者：
Glass, WG;Lane, TE
用小鼠肝炎病毒(MHV)感染C57BL/6小鼠，可导致急性脑脊髓炎和类似于人类多发性硬化症(MS)的脱髓鞘疾病。T细胞参与MHV感染后的防御和疾病进展。趋化因子受体在活化的T细胞上的表达在允许这些细胞进入并在感染MHV的小鼠的中枢神经系统(CNS)内积累方面是重要的。本研究评价了CCR5在病毒特异性CD8(+)T细胞活化和转运到感染MHV的CNS小鼠中的作用。过继转移MHV感染的RAG1(-/-)小鼠的中枢神经系统中，来自免疫的CCR5(+/+)或CCR5(-/-)小鼠的病毒特异性CD8(+)T细胞的数量相当，这表明CCR5不是运输这些细胞到中枢神经系统所必需的。接受CCR5(-/-)来源的CD8(+)T细胞的RAG1(-/-)受者表现出适度但显著(P小于或等于0.05)的脑内病毒载量的减少，这与CTL活性和干扰素-γ的表达增加有关。对接受CCR5(+/+)或CCR5(-/-)来源的CD8(+)T细胞的RAG1(-/-)受者的组织学分析显示，只有局限性的脱髓鞘区域，在白质破坏方面没有显著差异。这些数据表明，CD8(+)T细胞上的CCR5信号调节抗病毒活性，但不是进入中枢神经系统所必需的。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). T cells participate in both defense and disease progression following MHV infection. Expression of chemokine receptors on activated T cells is important in allowing these cells to traffic into and accumulate within the central nervous system (CNS) of MHV-infected mice. The present study evaluated the contributions of CCR5 to the activation and trafficking of virus-specific CD8(+) T cells into the MHV-infected CNS mice. Comparable numbers of virus-specific CD8(+) T cells derived from immunized CCR5(+/+) or CCR5(-/-) mice were present within the CNS of MHV-infected RAG1(-/-) mice following adoptive transfer, indicating that CCR5 is not required for trafficking of these cells into the CNS. RAG1(-/-) recipients of CCR5(-/-)-derived CD8(+) T cells exhibited a modest, yet significant (P less than or equal to 0.05), reduction in viral burden within the brain which correlated with increased CTL activity and IFN-gamma expression. Histological analysis of RAG1(-/-) recipients of either CCR5(+/+) or CCR5(-/-)-derived CD8(+) T cells revealed only focal areas of demyelination with no significant differences in white matter destruction. These data indicate that CCR5 signaling on CD8(+) T cells modulates antiviral activities but is not essential for entry into the CNS. (C) 2003 Elsevier Science (USA). All rights reserved.