效应器
生物
转录因子
细胞生物学
CD8型
免疫系统
免疫学
遗传学
基因
作者
Loreto Parga‐Vidal,Felix M. Behr,Natasja A. M. Kragten,Benjamin Nota,Thomas H. Wesselink,Inga Kavazović,Laura Covill,Margo B. P. Schuller,Yenan T. Bryceson,Felix M. Wensveen,René A. W. van Lier,Teunis J. P. van Dam,Regina Stark,Klaas P. J. M. van Gisbergen
出处
期刊:Science immunology
[American Association for the Advancement of Science]
日期:2021-08-10
卷期号:6 (62)
被引量:92
标识
DOI:10.1126/sciimmunol.abg3533
摘要
Tissue-resident memory CD8+ T cells (TRM) constitute a noncirculating memory T cell subset that provides early protection against reinfection. However, how TRM arise from antigen-triggered T cells has remained unclear. Exploiting the TRM-restricted expression of Hobit, we used TRM reporter/deleter mice to study TRM differentiation. We found that Hobit was up-regulated in a subset of LCMV-specific CD8+ T cells located within peripheral tissues during the effector phase of the immune response. These Hobit+ effector T cells were identified as TRM precursors, given that their depletion substantially decreased TRM development but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit+ effector T cells corroborated their biased contribution to the TRM lineage. Transcriptional profiling of Hobit+ effector T cells underlined the early establishment of TRM properties including down-regulation of tissue exit receptors and up-regulation of TRM-associated molecules. We identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of TRM occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.
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