Developmental plasticity allows outside-in immune responses by resident memory T cells

Abstract

Central memory T (T CM ) cells patrol lymph nodes and perform conventional memory responses upon re-stimulation: proliferation, migration, and differentiation into diverse T cell subsets while also self-renewing. Resident memory T (T RM ) cells are parked within single organs, share properties with terminal effectors, and contribute to rapid host protection. We observed that reactivated T RM cells rejoined the circulating pool. Epigenetic analyses revealed that T RM cells align closely with conventional memory T cell populations, bearing little resemblance to recently activated effectors. Fully differentiated T RM cells isolated from small intestine epithelium exhibited the potential to differentiate into T CM , T EM , and T RM cells upon recall. Ex-T RM cells, former intestinal T RM that rejoined the circulating pool, heritably maintained a predilection for homing back to their tissue of origin upon subsequent reactivation and a heightened capacity to re-differentiate into T RM cells. Thus, T RM cells can rejoin the circulation but are advantaged to re-form local T RM when called upon.

Tissue-resident CD8+T cells drive age-associated chronic lung sequelae following viral pneumonia

“…Thus, defective TCR-mediated effector cytokine production could underlie the impaired protection against secondary influenza virus infection. Notably, T RM cells can undergo in situ proliferation and generate secondary effector T cells [41, 57, 58]. Previously, it has been shown that memory T cells in aged mice are senescent in proliferation during secondary expansion [8].…”

Transcriptional profiling and single-cell chimerism analysis identifies human tissue resident T cells in the human skin after allogeneic stem cell transplantation

“…While the overall blood T cell population displayed a resting functional state, the host blood CD8+ T cell population displayed a strong enrichment of proliferating T cells according to the proportion of cells within the G2/M phase. It remains scarcely investigated whether and how TRM cells exit their tissue of origin 10,19. Based on our cell cycle analysis, we speculate that preceding T cell activation might have mobilized them out of their respective tissues.…”

Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program

“…Lymphocytes are thought to display common features inherent to the tissue in which they reside 21,39,44,45,46 . Consequently, migrating immune cells must be able to readily adapt to their new environment at the transcriptional level, although the type and speed of tissue-imprinting will vary with the tissue and the immune cell of interest 20,39,45,46,47,48,49,50 . For instance, it was proposed that while Tregs from skin and colon retain a common Treg program, they concomitantly acquire tissue-specific profiles 21 .…”

“…For instance, it was proposed that while Tregs from skin and colon retain a common Treg program, they concomitantly acquire tissue-specific profiles 21 . Conversely, studies characterizing TRM, which share several characteristics with IEL subsets, also observed a progressive acquisition of a tissue-specific transcriptional profile, distinct of circulating memory cells 46 .…”