Our observations show dual roles for mucosal CD4+ T cells following infection with C. rodentium in the colon: First, IL-21 was exclusively expressed by mucosal CD4+ T cells of the colon LP and second, mucosal CD4+ T cells express significant levels of transcripts for IL-21R and IFN-γR and are targets for the collaborative activity of IFN-γ and IL-21. Here, IFNGR1 is linked to infection.