T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells

Abstract

Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8 T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared some transcriptional and phenotypic signatures associated with nonlymphoid Trm cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells and suggest vaccination strategies by which memory CD8 T cell immunosurveillance can be regionalized to specific lymph nodes.

Molecular determinants and heterogeneity of tissue-resident memory CD8+ T lymphocytes revealed by single-cell RNA sequencing

“…This population also exhibited higher expression of transcripts encoding molecules that promote tissue retention, such as Cxcr3 and Klf3 (67). Taken together, these findings suggest that one TRM cell subset may exhibit a greater potential to leave the tissue and migrate to a draining lymph node in response to re-infection, where enhanced production of cytokines might promote the activation of circulating memory cells, which can then enter tissues and give rise to secondary TRM cells, as has been recently reported (68). By contrast, the second TRM cell subset might be more prone to remain within the tissue and mediate protective responses directly within the tissue microenvironment.…”

Functional delineation of tissue-resident CD8+ T cell heterogeneity during infection and cancer

“…In contrast, the Id3 hi KLRG1 lo CD127 hi siIEL CD8 + T cells appear to be tissueresident memory precursors (TRMP, during the effector phase of infection) or long-lived tissue-resident memory cells (TRM, during the memory phase of infection) as they share transcriptional signatures with other memory or memory-like populations (MP/TCM CD8 + T cells and TFH CD4 + T cells) and have increased memory potential and multipotency, with the capacity to generate circulating and TRM populations following re-infection. TRM can rapidly proliferate in situ following re-infection (Beura et al, 2018a;Park et al, 2018), and in certain contexts, may exit the tissue and rejoin the circulating memory pool (Beura et al, 2018b;Masopust et al, 2006). We propose that it is the more stem-like Id3 hi TRM subset that undergoes local proliferation during secondary infection and differentiates into the circulating ex-TRM population.…”

Resident memory CD8 T cells persist for years in human small intestine

“…CD103 was expressed by most (76%) LP CD8 T cells and by all IE CD8 T cells (Figure 1D), whereas the minor population of LP CD8 T cells lacking CD103 was more similar to PB CD8 T cells ( Figure 1C). Given that CD103 is the currently most established marker to infer residency at mucosal surfaces (Beura et al, 2018b) we evaluated the phenotypic profiles of CD103+ and CD103-SI CD8 T cells in a larger cohort of donors (Figure 2A). CD127 was expressed by a larger fraction of LP CD103+ CD8 T cells than IE CD103+ and LP CD103-CD8 T cells (Figure 2A).…”