INCREASED INTRACELLULAR TH1 CYTOKINES IN SCID MICE WITH INFLAMMATORY BOWEL-DISEASE

Severe combined immunodeficient (scid) mice engrafted with small piece s of full thickness gut wall from immunocompetent syngenic donors deve lop a chronic and lethal colitis. Lymphocytes from the lamina propria of engrafted mice were analyzed for phorbol ester/ionomycin-induced cy tokine production by intracellular staining. A 4-5-fold increase in th e fraction of IFN-gamma-producing CD4(+) lamina propria T cells was fo und 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 posi tive CD4(+) T cells was increased by a factor of two in both moderatel y and severely diseased mice. When analyzing Th2 cytokines, it was fou nd 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 health y control mice. No intracellular cytokines could be detected in lympho cytes not treated with phorbol ester/ionomycin. The present data ident ify a prominent role for Th1-type T helper cells in the immunopathogen esis of gut wall graft-induced inflammatory bowel disease in scid mice .