Local antigen is required for CD8+ tissue resident memory T cell (Trm) generation in large intestine
The specifying signals provided by the tissue microenvironment to promote acquisition of Trm features vary across anatomical niches, and those delivered in the large intestine (LI) remain largely uncharacterized. Here we show that following migration of activated T cells from the priming lymph nodes, antigen recognition in the tissue microenvironment is crucial to establish LI CD8 Trm. In the absence of tissue-confined antigen, T cells fail to generate memory precursors and to accumulate in the tissue. Local antigen presentation boosts Trm generation in a dose-dependent manner, and prompts transient acquisition of a distinctive transcriptional program including key signatures of gut Trm. The definitive transcriptional landscape of LI Trm cells comprises both features that are shared with Trm at other locations, as well as unique elements. Our findings identify antigen presentation in the gut microenvironment as a key step in the generation of large LI CD8 Trm, providing key insight for the optimization of mucosal immunization strategies. Overall design: Based on our previous study, to have a more comprehensive understanding of large intestine lamina propria (LILP) Trm cells, we established Listeria-OVA (Lm-OVA) oral infection model combining with OTI cell transfer. At day30, spleen memory OTI cells were sorted, followed by bulk RNA-seq. Thus, we can have a direct comparison between spleen memory T and LILP Trm cells.