sq-23377 and Inflammatory-Bowel-Diseases

Severe combined immunodeficient (scid) mice engrafted with small pieces of full thickness gut wall from immunocompetent syngenic donors develop a chronic and lethal colitis. Lymphocytes from the lamina propria of engrafted mice were analyzed for phorbol ester/ionomycin-induced cytokine production by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice suffering from severe disease to healthy control mice. The fraction of TNF-alpha positive CD4+ T cells was increased by a factor of two in both moderately and severely diseased mice. When analyzing Th2 cytokines, it was found that the levels of IL-4-producing CD4+ T cells was not altered in diseased animals, whereas the fraction IL-10-producing CD4+ T cells was reduced by a factor of 20. The combined data showed a 15-25-fold increase in the Th1/Th2 ratio of diseased mice when compared to healthy control mice. No intracellular cytokines could be detected in lymphocytes not treated with phorbol ester/ionomycin. The present data identify a prominent role for Th1-type T helper cells in the immunopathogenesis of gut wall graft-induced inflammatory bowel disease in scid mice.

Topics: Animals; Colon; Disease Models, Animal; Inflammatory Bowel Diseases; Interferon-gamma; Interleukin-10; Interleukin-4; Intestines; Ionomycin; Lymphokines; Mice; Mice, SCID; Tetradecanoylphorbol Acetate; Th1 Cells; Th2 Cells; Transplantation, Heterotopic; Tumor Necrosis Factor-alpha