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Gastroenterology. 1999 Feb;116(2):320-6.

The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice.

Author information

1
Immunopathology Unit, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

BACKGROUND & AIMS:

T-cell receptor alpha mutant (TCRalpha-/-) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by creating IL-4- or IFN-gamma-deficient TCRalpha-/- mice.

METHODS:

Double-mutant mice were created by crossing TCRalpha-/- mice with IL-4- or IFN-gamma-deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed.

RESULTS:

The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-gamma-/- x TCRalpha-/- mice developed colitis similar to that present in TCRalpha-/- mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCRalpha-/- mice and IFN-gamma-/- x TCRalpha-/- mice compared with IL-4(-/-) x TCRalpha-/- mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4(-/-) x TCRalpha-/- mice.

CONCLUSIONS:

IL-4 plays an important role in the development of colitis in TCRalpha-/- mice. In contrast, severe colitis in TCRalpha-/- mice can develop in the absence of IFN-gamma.

PMID:
9922312
DOI:
10.1016/s0016-5085(99)70128-9
[Indexed for MEDLINE]

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