Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes.
Sci Immunol
; 6(62)2021 08 20.
Article
en En
| MEDLINE
| ID: mdl-34417257
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD8-positivos
/
Proteínas de Dominio T Box
/
Células T de Memoria
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article