The Function of the Chemokine Receptor CXCR6 in the T Cell Response of Mice against Listeria monocytogenes

The chemokine receptor CXCR6 is expressed on different T cell subsets and up-regulated following T cell activation. CXCR6 has been implicated in the localization of cells to the liver due to the constitutive expression of its ligand CXCL16 on liver sinusoidal endothelial cells. Here, we analyzed the role of CXCR6 in CD8+ T cell responses to infection of mice with Listeria monocytogenes. CD8+ T cells responding to listerial antigens acquired high expression levels of CXCR6. However, deficiency of mice in CXCR6 did not impair control of the L. monocytogenes infection. CXCR6-deficient mice were able to generate listeria-specific CD4+ and CD8+ T cell responses and showed accumulation of T cells in the infected liver. In transfer assays, we detected reduced accumulation of listeria-specific CXCR6-deficient CD8+ T cells in the liver at early time points post infection. Though, CXCR6 was dispensable at later time points of the CD8+ T cell response. When transferred CD8+ T cells were followed for extended time periods, we observed a decline in CXCR6-deficient CD8+ T cells. The manifestation of this cell loss depended on the tissue analyzed. In conclusion, our results demonstrate that CXCR6 is not required for the formation of a T cell response to L. monocytogenes and for the accumulation of T cells in the infected liver but CXCR6 appears to influence long-term survival and tissue distribution of activated cells.趋化因子受体CXCR6 (chemokine receptor CXCR6)可表达于多种T细胞亚群，并在T细胞活化后出现表达上调。鉴于其配体趋化因子配体CXCL16 (CXCL16)在肝窦内皮细胞 (liver sinusoidal endothelial cells)上呈组成性表达，CXCR6被认为与细胞向肝脏的归巢相关。本研究中，我们分析了CXCR6在小鼠感染单核细胞增生李斯特菌 (Listeria monocytogenes)后的CD8阳性T细胞 (CD8+ T cell)应答中的作用。针对李斯特菌抗原产生应答的CD8阳性T细胞会高表达CXCR6。然而，小鼠CXCR6缺陷并不会削弱机体对单核细胞增生李斯特菌感染的控制能力。CXCR6缺陷小鼠能够产生针对李斯特菌的特异性CD4阳性T细胞 (CD4+ T cell)和CD8阳性T细胞应答，且可观察到T细胞在感染肝脏内的聚集。在过继转移实验中，我们检测到感染后早期时点，针对李斯特菌的特异性CXCR6缺陷型CD8阳性T细胞在肝脏内的聚集量有所减少。不过在CD8阳性T细胞应答的后期阶段，CXCR6并非必需。当对过继转移的CD8阳性T细胞进行长期追踪时，我们发现CXCR6缺陷型CD8阳性T细胞的数量出现下降。这种细胞丢失的表现特征取决于所分析的组织类型。综上，本研究结果表明，CXCR6并非小鼠针对单核细胞增生李斯特菌产生T细胞应答以及T细胞在感染肝脏内聚集所必需的分子，但CXCR6似乎可影响活化T细胞的长期存活及组织分布。