The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/4/1169/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 8, April 19, 1999 1169-1180

Articles

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

Taeko Dohi*, Kohtaro Fujihashi*,{ddagger}, Paul D. Rennert§, Koichi Iwatani, Hiroshi Kiyono*,{ddagger},¶, and Jerry R. McGhee*

From the * Immunobiology Vaccine Center, Department of Microbiology and {ddagger} 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

Address correspondence to Dr. Jerry R. McGhee, The Immunobiology Vaccine Center and the Department of Microbiology, the University of Alabama at Birmingham, 761 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, AL 35294-2170. Phone: 205-934-5045; Fax: 205-975-4431; E-mail: mcghee{at}uab.edu

Abbreviations used: GALT, gut-associated lymphoreticular tissues; IBD, inflammatory bowel diseases; PNA, peanut agglutinin; SLN, sacral lymph nodes; TNBS, 2,4,6-trinitrobenzene sulfonic acid.


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