Small intestine and colon tissue-resident memory CD8+T cells exhibit molecular heterogeneity and differential dependence on Eomes

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. TRM cells exhibit differences across tissues, but their po-tential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing TRM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal TRM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses TRM cell formation in some tissues, exhibited un-expected context-specific regulatory roles in supporting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal TRM cells.

Automated summary

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that are important for controlling infection. TRM cells in the small intestine and colon exhibit heterogeneity in terms of cytokine and granzyme expression, transcriptional and epigenetic regulation, and functional characteristics. The transcription factor Eomes plays a context-specific role in supporting the maintenance of established TRM cells in the small intestine but not in the colon.