The Journal of Experimental Medicine
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J. Exp. Med., Volume 189, Number 8, April 19, 1999 1169-1180

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

By Taeko Dohi,* Kohtaro Fujihashi,*Dagger Paul D. Rennert,§ Koichi Iwatani, Hiroshi Kiyono,*Dagger and Jerry R. McGhee*

From the * Immunobiology Vaccine Center, Department of Microbiology and Dagger  Department of Oral Biology,  The University of Alabama at Birmingham, Birmingham, Alabama 35294; § Biogen Incorporated, Cambridge, Massachusetts 02142; and the  Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan

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)-gamma synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-gamma +/+) or Th1-deficient IFN-gamma knockout (IFN-gamma -/-) BALB/c mice resulted in significant colitis. In IFN-gamma -/- mice, crypt inflammation was more severe than in IFN-gamma +/+ 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-gamma +/+ or IFN-gamma -/- 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.

Key words: inflammatory bowel diseases;  mouse T cells;  cytokines;  hapten-induced colitis


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