Distinct LLO-specific CD4 T cells infiltrate the intestinal mucosa following oral Listeria monocytogenes infection. (P3224)

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Abstract Listeria monocytogenes (LM) is an enteroinvasive pathogen and the cause of listeriosis, a highly fatal foodborne infection. Using an oral LM infection model, we show that a subset of blood-borne listeriolysin O (LLO)-specific CD4 T cells transiently expressed the α4β7 integrin early after infection. Antigen-specific CD4 T cells rapidly accumulated in the mucosa and mounted a robust recall response following secondary infection. On day 9 post LM infection, LLO-specific CD4 T cells in the mucosa are almost exclusively Ly6Clow/CD27low and this population persists throughout memory. In contrast, LLO-specific CD4 T cells isolated from the spleen and MLN were heterogenous for CD27 and Ly6C expression. Mucosal LLO-specific CD27lowLy6ClowCD4 T cells produced IFN-γ and IL-2 and a small subset also produced IL-17. Interestingly, IL-17 production increased in mucosal memory CD4 T cells. Furthermore, IL-17 production was increased in mucosal CD4 T cells in CD69-deficient mice. However, mixed bone marrow chimera studies indicated that this phenomenon is independent ofCD69 expression on responding CD4 T cells. Depletion of CD4 T cells during memory led to higher bacterial burden in the gut and spleen. These results indicate that mucosal effector and memory CD4 T cells are phenotypically and functionally distinct from their splenic counterparts. Thus, our findings demonstrate an important role for mucosal memory CD4 T cells in protection against oral infection.