CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.
CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.
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DOI：
10.4049/jimmunol.1500993
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Khanna KM
中科院分区：
文献类型：
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作者：
Sharma N;Benechet AP;Lefrançois L;Khanna KM
CCR 7是一种重要的趋化因子受体，其调节次级淋巴器官内的T细胞运输和区室化。然而，CCR 7在脾脏感染过程中的T细胞内在作用尚不清楚。本研究旨在了解CCR 7依赖性CD 8 + T细胞在脾脏不同区室中的定位和迁移如何影响感染后的初次和回忆反应。为此，我们在随后用单核细胞增生李斯特菌（Lm）静脉内感染的小鼠中利用缺乏CCR 7或组成型表达CCR 7（CD 2-CCR 7）的幼稚抗原特异性CD 8 T细胞（OT-I）的过继转移。我们发现，初始CCR 7 −/− CD 8 + T细胞未能进入T细胞区，而CD 2-CCR 7 OT-I细胞仅限于脾脏的T细胞区。然而，令人惊讶的是，CCR 7-/-OT-I细胞在感染后进入T细胞区，但这些细胞的进入和外出迁移模式失调，与WT OT-I细胞相比非常不同。此外，当与WT OT-I细胞相比时，CCR 7缺陷型OT-I细胞不能稳健地扩增，并且优先偏向于短寿命效应细胞（SLEC）分化模式。有趣的是，CCR 7 −/−、CD 2-CCR 7和WT OT-I记忆细胞对再攻击感染的反应同样良好。这些结果突出了CCR 7在调节脾脏中效应CD 8 T细胞迁移中的新作用，并证明了CCR 7对感染的初级和次级CD 8 T细胞应答的不同需求。
CCR7 is an important chemokine receptor which regulates T cell trafficking and compartmentalization within secondary lymphoid organs. However, the T cell intrinsic role of CCR7 during infection in the spleen is not well understood. This study was designed to understand how CCR7 dependent localization and migration of CD8+ T cells in different compartments of spleen affected the primary and recall responses after infection. To this end we utilized adoptive transfer of naive antigen specific CD8 T cells (OT-I) that either lacked CCR7 or constitutively expressed CCR7 (CD2-CCR7) in mice that were subsequently infected intravenously with Listeria monocytogenes (Lm). We show that naive CCR7−/− CD8+ T cells failed to enter the T cell zone, while CD2-CCR7 OT-I cells were exclusively confined to the T cell zones of the spleen. However, surprisingly CCR7−/− OT-I cells entered the T cell zones after infection, but the entry and egress migratory pattern of these cells was dysregulated and very distinct compared to WT OT-I cells. Moreover, CCR7 deficient OT-I cells failed to expand robustly when compared to WT OT-I cells and were preferentially skewed towards a short-lived effector cells (SLEC) differentiation pattern. Interestingly, CCR7−/−, CD2-CCR7 and WT OT-I memory cells responded equally well to rechallenge infection. These results highlight a novel role of CCR7 in regulating effector CD8 T cell migration in the spleen and demonstrate differential requirement of CCR7 for primary and secondary CD8 T cell responses to infection.