CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system
CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system
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DOI：
10.4049/jimmunol.176.7.4235
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发表时间：
2006-04-01
影响因子：
4.4
通讯作者：
Thomsen, Allan Randrup
中科院分区：
文献类型：
--
作者：
Christensen, Jeanette Erbo;de Lemos, Carina;Thomsen, Allan Randrup
IFN-γ诱导蛋白10/CXCL 10是与1型T细胞应答相关的趋化因子，通过与CXCR 3受体结合来调节活化T细胞的迁移。在CNS的免疫病理学疾病期间观察到CXCL 10和CXCR 3的表达，并且认为该受体/配体对在调节该器官部位中的T细胞介导的炎症中起核心作用。在这份报告中，我们研究了CXCL 10在调节病毒感染脑中CD 8（+）T细胞介导的炎症中的作用。这是通过分析CXCL 10缺陷小鼠脑内感染淋巴细胞性脉络丛脑膜炎病毒来完成的，在正常免疫活性小鼠中，该病毒诱导致命的CD 8（+）T细胞介导的脑膜脑炎。我们发现CXCL 10缺陷小鼠产生了正常的抗病毒CD 8（+）T细胞应答，并且CXCL 10的缺乏对脑脊液中单核细胞的积累没有影响。然而，对CXCL 10缺陷小鼠对淋巴细胞性脉络丛脑膜炎病毒诱导的脑膜炎的易感性的分析显示，这些小鼠就像CXCR 3缺陷小鼠一样对这种疾病具有部分抗性，而野生型小鼠总是死亡。此外，尽管剩下的两个CXCR 3配体：CXCL 9和11显著上调，我们发现当野生型小鼠因CD 8（+）T细胞介导的炎症而死亡时，脑实质中CD 8（+）T细胞的积累减少。因此，综合这些结果表明，CXCL 10在调节效应T细胞在CNS炎症部位的积累中具有中心作用，而其他CXCR 3配体没有明显的代偿作用。
IFN-gamma-inducible protein 10/CXCL10 is a chemokine associated with type 1 T cell responses, regulating the migration of activated T cells through binding to the CXCR3 receptor. Expression of both CXCL10 and CXCR3 are observed during immunopathological diseases of the CNS, and this receptor/ligand pair is thought to play a central role in regulating T cell-mediated inflammation in this organ site. In this report, we investigated the role of CXCL10 in regulating CD8(+) T cell-mediated inflammation in the virus-infected brain. This was done through analysis of CXCL10-deficient mice infected intracerebrally with lymphocytic choriomeningitis virus, which in normal immunocompetent mice induces a fatal CD8(+) T cell-mediated meningoencephalitis. We found that a normal antiviral CD8(+) T cell response was generated in CXCL10-deficient mice, and that lack of CXCL10 had no influence on the accumulation of mononuclear cells in the cerebrospinal fluid. However, analysis of the susceptibility of CXCL10-deficient mice to lymphocytic choriomeningitis virus-induced meningitis revealed that these mice just like CXCR3-deficient mice were partially resistant to this disease, whereas wild-type mice invariably died. Furthermore, despite marked up-regulation of the two remaining CXCR3 ligands: CXCL9 and 11, we found a reduced accumulation of CD8(+) T cells in the brain parenchyma around the time point when wild-type mice succumb as a result of CD8(+) T cell-mediated inflammation. Thus, taken together these results indicate a central role for CXCL10 in regulating the accumulation of effector T cells at sites of CNS inflammation, with no apparent compensatory effect of other CXCR3 ligands.