Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease.
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.
Bregenholt
S
S
Department of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark. s.bregenholt@mai.ku.dk
Claesson
M H
MH
D000818:Animals; D003106:Colon / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007422:Intestines / Q000637:transplantation; D015759:Ionomycin / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D016513:Mice, SCID; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism; D016042:Transplantation, Heterotopic / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate