Aggravation of intestinal inflammation by depletion/deficiency of γδ T cells in different types of IBD animal models

Abstract The role of γδ T cells in inflammatory bowel disease (IBD) is still controversial. Although γδ T cells induce IBD in immunodeficient animals, others suggest a protective role of γδ T cells. Therefore, this study was conducted in order to elucidate the effect of γδ T cell depletion/deficiency on different IBD animal models. Mice depleted of or deficient in γδ T cells were exposed to dextran sodium sulfate (DSS) in order to induce colitis. In addition, γδ T cells were depleted in mice with terminal ileitis (TNFΔARE) or colitis due to interleukin 2 deficiency (IL-2 ko). Finally, DSS-induced colitis was studied in mice deficient in interferon gamma (IFN-γ ko) upon γδ T cell depletion. Depletion of γδ T cells aggravated DSS-induced colitis and terminal ileitis of TNFΔARE mice. Exacerbated DSS-induced colitis was also found in γδ T cell-deficient mice. IL-2 ko mice showed increased mortality upon early (starting at 4 wk of age) but not late depletion (starting at 8 wk of age). Early γδ T cell depletion or deficiency resulted in increased IFN-γ production by both lamina propria lymphocytes and splenocytes in every model investigated herein. In IFN-γ ko mice, γδ T cell depletion did not affect the development and course of DSS-induced colitis. The protective effect of γδ T cells in IBD was confirmed in various IBD animal models. Particularly, during the early phase of intestinal inflammation, γδ T cells appear to be important. The mechanism seems to involve the control of IFN-γ production and epithelial regeneration.