TY - JOUR
T1 - Treatment of experimental colitis by oral tolerance induction
T2 - A central role for suppressor lymphocytes
AU - Ilan, Yaron
AU - Weksler-Zangen, Sarah
AU - Ben-Horin, Shomron
AU - Diment, Judith
AU - Sauter, Bernhard
AU - Rabbani, Elazar
AU - Engelhardt, Dean
AU - Roy Chowdhury, Namita
AU - Roy Chowdhury, Jayanta
AU - Goldin, Eran
N1 - Funding Information:
This work was supported in part by grants from The United States-Israel Binational Science Foundation 0060 (to Y.I. and J.R.C.). Additional support was provided by a grant from Hadasit-Yissum (to Y.I.), a grant from ENZO Biochem Inc., NY (to Y.I.); and grants ROI-DK 46057 (to J.R.C.), RO1-DK 39137 (to N.R.C.), and P30-DK 41296 (Liver Research Core Center, to J.R.C.).
PY - 2000/4
Y1 - 2000/4
N2 - OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.
AB - OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.
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U2 - 10.1016/S0002-9270(00)00727-9
DO - 10.1016/S0002-9270(00)00727-9
M3 - Article
C2 - 10763946
AN - SCOPUS:16744365988
SN - 0002-9270
VL - 95
SP - 966
EP - 973
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 4
ER -
