Heterogenous Populations of Tissue-Resident CD8

Tissue-resident memory CD8(+) T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8(+) T cells, including a Blimp1(hi)Id3(lo) tissue-resident effector cell population, most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1 (lo)Id3(hi) tissue-resident memory population that subsequently accumulated at later infection timepoints. These Trm populations exhibited distinct cytokine production, secondary memory potential, and transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8(+) T cell populations with tissue-resident gene-expression signatures that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Our findings provide insight into the development and functional heterogeneity of Trm cells, with implications for enhancing vaccination and immunotherapy approaches.