CXCR3-dependent recruitment of antigen-specific T lymphocytes to the liver during murine cytomegalovirus infection
CXCR3-dependent recruitment of antigen-specific T lymphocytes to the liver during murine cytomegalovirus infection
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DOI：
10.1128/jvi.01937-06
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Salazar-Mather, Thais P.
中科院分区：
文献类型：
--
作者：
Hokeness, Kirsten L.;Deweerd, Elizabeth S.;Salazar-Mather, Thais P.
先天性炎症事件促进肝脏抗鼠巨细胞病毒（MCMV）感染的抗病毒防御已被表征。然而，在MCMV感染期间，调节炎性T淋巴细胞向肝脏选择性募集的机制尚未确定。本文所述的研究证明了γ干扰素（IFN-γ; Mig/CXCL 9）和IFN-γ诱导蛋白10（IP-10/CXCL 10）诱导的单核因子在肝白细胞中的表达，并将其产生与MCMV特异性CD 8 T细胞向肝中的浸润相关联。CXCL 9和CXCL 10的抗体介导的中和以及使用CXCR 3（这些趋化因子的主要已知受体）缺陷的小鼠的研究揭示了CXCR 3依赖性机制在MCW急性感染期间促进病毒特异性CD 8 T细胞浸润到肝脏中。此外，CXCR 3功能增强了对MCMV的CD 8 T细胞IFN-γ应答的肝脏积累。对保护功能的评价表明，CXCR 3缺陷小鼠的病理学增强与病毒滴度的短暂增加重叠。然而，最终的病毒清除率和存活率没有受到影响。因此，CXCR 3介导的信号支持MCMV特异性CD 8 T细胞的积累，这些细胞有助于病毒感染组织部位的保护性应答，但不是唯一需要的。
Innate inflammatory events promoting antiviral defense in the liver against murine cytomegalovirus (MCMV) infection have been characterized. However, the mechanisms that regulate the selective recruitment of inflammatory T lymphocytes to the liver during MCMV infection have not been defined. The studies presented here demonstrate the expression of monokine induced by gamma interferon (IFN-gamma; Mig/CXCL9) and IFN-gamma-inducible protein 10 (IP-10/CXCL10) in liver leukocytes and correlate their production with the infiltration of MCMV-specific CD8 T cells into the liver. Antibody-mediated neutralization of CXCL9 and CXCL10 and studies using mice deficient in CXCR3, the primary known receptor for these chemokines, revealed that CXCR3-dependent mechanisms promote the infiltration of virus-specific CD8 T cells into the liver during acute infection with MCW. Furthermore, CXCR3 functions augmented the hepatic accumulation of CD8 T-cell IFN-gamma responses to MCMV. Evaluation of protective functions demonstrated enhanced pathology that overlapped with transient increases in virus titers in CXCR3-deficient mice. However, ultimate viral clearance and survival were not compromised. Thus, CXCR3-mediated signals support the accumulation of MCMV-specific CD8 T cells that contribute to, but are not exclusively required for, protective responses in a virus-infected tissue site.