Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells.
Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells.
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抗原依赖性竞争塑造了组织居民记忆CD8+ T细胞的局部曲目。
DOI：
10.1084/jem.20160888
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发表时间：
2016-12-12
期刊：
影响因子：
--
通讯作者：
Gasteiger G
中科院分区：
文献类型：
--
作者：
Muschaweckh A;Buchholz VR;Fellenzer A;Hessel C;König PA;Tao S;Tao R;Heikenwälder M;Busch DH;Korn T;Kastenmüller W;Drexler I;Gasteiger G
Muschaweckh等人表明，皮肤中的抗原呈递通过协调抗病毒CD8+ T细胞的局部竞争来调节组织驻留记忆T （TRM）细胞的产生，揭示了一种微调区域TRM细胞库的机制。组织驻留记忆CD8+ T细胞（TRM）是非淋巴器官免疫监视系统的重要组成部分。在组织浸润性T细胞中，局部、非同源因子是支持TRM细胞命运编程的必要和充分因素。最近的证据表明，受感染的非淋巴组织接收的TCR信号也有助于TRM细胞的形成。在这里，我们询问抗原依赖途径如何影响皮肤驻留记忆T细胞的产生，这些T细胞是由抗原复杂病毒和重组疫苗载体感染诱导的多克隆细胞库产生的。我们发现不同特异性的CD8+ T细胞在感染组织中进行抗原依赖性竞争，从而形成了局部TRM细胞池的组成。这种局部交叉竞争对识别被感染细胞共表达的抗原的T细胞是活跃的。相比之下，当在同一组织中表达的抗原通过抗原特异性不同的病毒准种感染分离时，TRM细胞的发育在很大程度上不受潜在竞争对手的影响。在功能上，局部交叉竞争可能作为一种守门机制来调节进入常驻记忆生态位的途径，并微调抗病毒TRM细胞的局部曲目。
Muschaweckh et al. show that antigen presentation in the skin regulates the generation of tissue-resident memory T (TRM) cells by orchestrating local competition of antiviral CD8+ T cells, revealing a mechanism to fine-tune the repertoire of regional pools of TRM cells. Tissue-resident memory CD8+ T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector. We found that CD8+ T cells of different specificities underwent antigen-dependent competition in the infected tissue, which shaped the composition of the local pool of TRM cells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, TRM cell development remained largely undisturbed by the presence of potential competitors when antigens expressed in the same tissue were segregated through infection with antigenically distinct viral quasispecies. Functionally, local cross-competition might serve as a gatekeeping mechanism to regulate access to the resident memory niche and to fine-tune the local repertoire of antiviral TRM cells.
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影响因子：
16.8
作者：
Iijima N;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
64.8
作者：
Jiang, Xiaodong;Clark, Rachael A.;Liu, Luzheng;Wagers, Amy J.;Fuhlbrigge, Robert C.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
8
作者：
Manrique, M.;Kozlowski, P. A.;Aldovini, A.
通讯作者：
Aldovini, A.
影响因子：
30.5
作者：
Mackay, Laura K.;Rahimpour, Azad;Gebhardt, Thomas
通讯作者：
Gebhardt, Thomas
非淋巴组织中的局部抗原促进了病毒感染期间居民记忆CD8+ T细胞的形成。
DOI：
10.1084/jem.20151855
发表时间：
2016-05-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khan TN;Mooster JL;Kilgore AM;Osborn JF;Nolz JC
通讯作者：
Nolz JC