A number of studies have identified the cytolytic mechanism underlying NK cell-mediated killing of autoreactive T cells, and the NK cell-mediated immunoregulatory activity was shown to be perforin-dependent in animal models of colitis, EAE, and CIA (Fort et al., 1998; Lu et al., 2007; Leavenworth et al., 2011). This evidence concerns the gene PRF1 and colitis.