BACKGROUND: Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized. METHODS: T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitis patients. RESULTS: In all groups the expression of interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha), and IL-2R beta messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2R alpha and IL-2R beta mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2R alpha and IL-2R beta mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2R alpha serum levels reflect gut T-cell hyperactivity in this disease. CONCLUSIONS: These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.
BACKGROUND:Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized. METHODS: T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitispatients. RESULTS: In all groups the expression of interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha), and IL-2R beta messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2R alpha and IL-2R beta mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2R alpha and IL-2R beta mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2R alpha serum levels reflect gut T-cell hyperactivity in this disease. CONCLUSIONS: These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.
Authors: K Sawada; K Ohnishi; S Fukui; K Yamada; M Yamamura; K Amano; K Amano; M Wada; N Tanida; M Satomi Journal: J Gastroenterol Date: 1995-06 Impact factor: 7.527
Authors: K Morise; T Yamaguchi; A Kuroiwa; K Kanayama; T Matsuura; M Shinoda; H Yamamoto; Y Horiuchi; A Furusawa; H Iwase Journal: J Gastroenterol Date: 1994-06 Impact factor: 7.527