UC San Diego

Tissue-resident memory (TRM) CD8+ T cells are a non-circulating subset of memory T cells that reside within barrier tissues and provide rapid and sustained host defense against reinfections. Recent studies have revealed that the location at which T cells are activated influences their trafficking patterns and cell fates. However, these findings often investigate T cells following memory formation, whereby the time and location of memory T cell fate divergence is not well characterized. By analyzing CD8+ T cells in the spleen, mesenteric lymph nodes, and small intestines using flow cytometry, I showed that the mesenteric lymph node exhibited a CCR9hi CD62Llo and a CD62Lhi CCR9lo population, with the former bearing phenotypic resemblance to bona fide gut-TRM cells and the latter to circulating memory T cells at 4 days post-infection. These findings suggest that memory T cells begin to specify their cell fates in the draining lymph node during early infection, prior to tissue entry. Additionally, I showed that the transcription factor TCF1, known to promote circulating memory T cell differentiation, is required for the formation of all memory precursors. These findings provide additional insight toward our understanding of the early signals that influence CD8+ T cell fate specification, serving as plausible treatments to tissue-specific or systemic infections.