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An inflammatory bowel disease (IBD) comparable to human ulcerative colitis is induced upon transfer of T cell-depleted wild-type (F1) bone marrow into syngeneic T cell-deficient (tgε26) mice (F1→tgε26). Previously we have shown that activated CD4 + T cells predominate in transplanted tgε26 mice, and adoptive transfer experiments verified the potential of these cells to cause disease in immunodeficient recipient mice. Using flow cytometry for the detection of intracellular cytokine expression, we demonstrate in the present study that large numbers of CD4 + and CD8 + TCRαβ + T cells from the intraepithelial region and lamina propria of the colon of diseased, but not from disease-free mice, produced interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Large numbers of T cells from peripheral lymphoid tissues of these animals also expressed IFN-γ and TNF-α, but few expressed interleukin-4, demonstrating a strong bias towards Th1-type T cell responses in these animals. TCRγδ + T cells, typically minor constituents of the inflammatory infiltrate of the colon in F1→tgε26 mice, also expressed IFN-γ at a high frequency upon CD3 stimulation. In light of these findings we examined the potential involvement of TCRγδ + T cells by testing their ability to induce colitis in tgε26 mice. We report here that tgε26 mice transplanted with T cell-depleted bone marrow from TCRα(null) and TCRβ(null) animals developed IBD. Furthermore, disease in these mice correlated with the development of peripheral and colonic TCRγδ + T cells capable of IFN-γ production. These results suggest that IFN-γ may be a common mediator of IBD utilized by pathogenic T cells of distinct phenotype.

Original publication

DOI

10.1002/eji.1830270104

Type

Journal article

Journal

European Journal of Immunology

Publication Date

01/01/1997

Volume

27

Pages

17 - 25