期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 13, 页码 3075-3086出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20160888
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG) [TRR128, SFB1054-B07]
- SyNergy
- DFG Excellence Cluster ImmunoSensation [SFB670, SFB704]
- DFG Emmy Noether program
- DFG [GRK 1949]
- European Research Council [CoG 647215]
- NRW-Ruckkehrerprogram of the German state of Northrhine-Westfalia
- TUM Foundation Fellowship
Tissue-resident memory CD8(+) T cells (T-RM) 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 T-RM cells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, T-RM 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 T-RM cells.
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