Citrobacter rodentium Induces Tissue-Resident Memory CD4 + T Cells

Tissue resident memory (T RM ) T-cells are a novel population of tissue restricted antigen specific T-cells. T RM are induced by pathogens and promote host-defense to secondary infections. Although T RM cells cannot be detected in circulation, they are the major memory CD4 + and CD8 + T-cell population in tissues in mice and humans. Murine models of CD8 + T RM cells have shown that CD8 + T RM cells maintain tissue residency via CD69 and though tumor growth factor β dependent induction of CD103. In contrast to CD8 + T RM cells, there are few models of CD4 + T RM cells. Thus, much less is known about the factors regulating the induction, maintenance and host-defense functions of CD4 + T RM cells. Citrobacter rodentium is known to induce IL-17 + and IL-22 + CD4 + T-cells (‘T h 17′ and ‘T h 22′ cells, respectively). Moreover, data from IL-22 reporter mice shows that most IL-22 + cells in the colon 3 months post- C. rodentium are CD4 + T-cells. This, collectively suggests that C. rodentium may induce CD4 + T RM cells. Herein, we demonstrated that C. rodentium induces a population of IL-17A + CD4 + T cells that are tissue restricted and antigen specific thus meeting the criteria of CD4 + T RM cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T-cells but not tissue restricted T-cells, we show that these CD4 + T RM cells can promote host defense.