Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes.
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 TGFbeta1 and a decrease in IFNgamma 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.
Ilan
Y
Y
Gastroenterology Unit, Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Weksler-Zangen
S
S
Ben-Horin
S
S
Diment
J
J
Sauter
B
B
Rabbani
E
E
Engelhardt
D
D
Chowdhury
N R
NR
Chowdhury
J R
JR
Goldin
E
E
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D003888:Desensitization, Immunologic; D015536:Down-Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D011506:Proteins / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014020:Tissue Extracts / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid
D011506:Proteins; D014020:Tissue Extracts; D014302:Trinitrobenzenesulfonic Acid