Hapten-induced Colitis Is Associated with Colonic Patch Hypertrophy and T Helper Cell 2–Type Responses

Abstract

To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory bowel disease in situations where Th1-type responses with interferon (IFN)-γ synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-γ+/+) or Th1-deficient IFN-γ knockout (IFN-γ−/−) BALB/c mice resulted in significant colitis. In IFN-γ−/− mice, crypt inflammation was more severe than in IFN-γ+/+ mice and was accompanied by hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice treated with anti–IL-4 antibodies or in IL-4−/− mice was less severe than in either IFN-γ+/+ or IFN-γ−/− mice. Our findings now show that the Th2-type responses in TNBS colitis are associated with colonic patch enlargement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.