Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses.
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.
Dohi
T
T
Immunobiology Vaccine Center, Department of Microbiology, University of Alabama at Birmingham, Alabama, USA.
Fujihashi
K
K
Rennert
P D
PD
Iwatani
K
K
Kiyono
H
H
McGhee
J R
JR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D006241:Haptens; D006984:Hypertrophy / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid
D000906:Antibodies; D006241:Haptens; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid