The development of IBD-like intestinal inflammation in Gimap5-deficient mice exhibits hallmark features of IBD development in humans that include (1) a critical role for microbial flora; (2) colitis that is CD4+ T cell driven; and (3) a concomitant loss of immunological tolerance, exemplified by a progressive decline in regulatory T cells (Treg) numbers and function. Here, CD4 is linked to inflammatory bowel disease.