Distinct LLO-specific CD4 T cells infiltrate the intestinal mucosa following oral Listeria monocytogenes infection. (49.16)

Abstract

Abstract We analyzed the mucosal CD4 T cell response to oral Listeria monocytogenes (LM) infection. Early after infection, a subset of blood-borne LLO-specific CD4 T cells expressed α4β7. Subsequently, antigen-specific CD4 T cells accumulated in the lamina propria and intraepithelial lymphocyte compartment where they were retained long-term. These data suggested that priming in the mucosal lymphoid tissues generated mucosa-seeking CD4 T cells with high memory potential. While naïve CD4 T cells contained both Ly6Chigh/CD27high and Ly6Clow/CD27high subsets, most primary and memory mucosal LLO-specific CD4 T cells were Ly6Clow/CD27low. In contrast, LLO-specific CD4 T cells in the spleen and MLN were comprised of four subsets based on CD27 and Ly6C expression. Upon challenge, mucosal CD4 T cells phenotypically resembled those in the primary infection, except for the appearance of a PD-1+ subset. Mucosal CD27low Ly6Clow and splenic CD27lowLy6Clow or high CD4 T cells either produced both IFN-γ and IL-2 or IFNγ alone and little IL-17 was detected. These results indicated that antigen-specific intestinal effector and memory CD4 T cells were phenotypically and functionally distinct from their lymphoid counterparts. Furthermore, the distinct phenotype of mucosal memory CD4 T cells implied that these cells may not recirculate. The generation of mucosal memory CD4 T cells in response to oral infection suggested a potential protective role for these cells in maintaining barrier infection.