Local antigen encounter promotes generation of tissue-resident memory T cells in the large intestine

Upon infection, CD8+ T cells that have been primed in the draining lymph nodes migrate to the invaded tissue, where they receive cues prompting their differentiation into tissue-resident memory cells (Trm), which display niche-specific transcriptional features. Despite the importance of these cells, our understanding of their molecular landscape and the signals that dictate their development remains limited, particularly in specific anatomical niches such as the large intestine (LI). Here, we report that LI Trmgenerated following oral infection exhibits a distinct transcriptional profile compared to Trm in other tissues. Notably, we observe that local cues play a crucial role in the preferential establishment of LI Trm, favoring precursors that migrate to the tissue early during infection. Our investigations identify cognate antigen recognition as a major driver of Trm differentiation at this anatomical site. Local antigen presentation not only promotes the proliferation of effector cells and memory precursors but also facilitates the acquisition of transcriptional features characteristic of gut Trm. Thus, antigen recognition in the LI favors the establishment of Trm by impacting T cell expansion and gene expression.