Naslov
Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes

Autori
Parga-Vidal, Loreto ; Behr, Felix M. ; Kragten, Natasja A. M. ; Nota, Benjamin ; Wesselink, Thomas H. ; Kavazović, Inga ; Covill, Laura E. ; Schuller, Margo B. P. ; Bryceson, Yenan T. ; Wensveen, Felix M. ; van Lier, Rene A. W. ; van Dam, Teunis J. P. ; Stark, Regina ; van Gisbergen, Klaas P. J. M.

Izvornik
Science Immunology (2470-9468) 6 (2021), 62; Eabg3533, 17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Hobit, Eomes, memory T cell

Sažetak
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.

Izvorni jezik
Engleski

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