Oral L. monocytogenes infection preferentially imprints memory precursor CD8 T cells for gut retention (161.10)

Abstract

Abstract The intestinal mucosa contains unique sites designed for antigen presentation and promotion of primary and memory CD8 T cell responses. Thus, generation of adaptive immunity within distinct tissues likely results in T cell responses with specific cellular outcomes. Here, we utilized an oral Listeria monocytogenes (LM) infection model in which internalin A is modified to promote invasion of murine intestinal epithelial cells. Oral infection induced a robust CD8 T cell response. In peripheral nonmucosal tissues, the majority of LM-specific CD8 T cells are short-lived effector cells (CD127- KLRG1+). Surprisingly, the majority of effector CD8 T cells in the intestinal mucosa are memory precursor effector cells (MPEC; CD127+ KLRG1-) early following oral infection. This effect appears to be due to preferential infiltration and retention of MPECs in intestinal tissues. CD103 (integrin αE), which is thought to be vital for retention of intestinal epithelial lymphocytes within the epithelium, was almost exclusively expressed by MPECs. The generation of distinct CD8 T cell subsets uniquely tailored to respond to intestinal pathogens early following infection may be a hallmark of oral challenge. Indeed, CD8 T cells that infiltrate the intestinal mucosa following intranasal influenza virus infection are early effector cells (CD127- KLRG1-), but failed to be maintained long-term, demonstrating the importance of intestinal priming for generating robust mucosal memory CD8 T cells.