title: Expression of dual TCR on DO11.10 T cells allows for ovalbumin-induced oral tolerance to prevent T cell-mediated colitis directed against unrelated enteric bacterial antigens.
abstract: The triggering Ag for inflammatory bowel disease and animal models of colitis is not known, but may include gut flora. Feeding OVA to DO11.10 mice with OVA-specific transgenic (Tg) TCR generates Ag-specific immunoregulatory CD4(+) T cells (Treg) cells. We examined the ability of oral Ag-induced Treg cells to suppress T cell-mediated colitis in mice. SCID-bg mice given DO11.10 CD4(+)CD45RB(high) T cells developed colitis, and cotransferring DO11.10 CD45RB(low)CD4(+) T cells prevented CD4(+)CD45RB(high) T cell-induced colitis in the absence of OVA. The induction and prevention of disease by DO11.10 CD4(+) T cell subsets were associated with an increase in endogenous TCRalpha chain expression on Tg T cells. Feeding OVA to SCID-bg mice reconstituted with DO11.10 CD4(+)CD45RB(high) attenuated the colitis in association with increased TGF-beta and IL-10 secretion, and decreased proliferative responses to both OVA and cecal bacteria Ag. OVA feeding also attenuated colitis in SCID-bg mice reconstituted with a mix of BALB/c and DO11.10 CD45RB(high) T cells, suggesting that OVA-induced Treg cells suppressed BALB/c effector cells. The expression of endogenous non-Tg TCR allowed for DO11.10-derived T cells to respond to enteric flora Ag. Furthermore, feeding OVA-induced Treg cells prevented colitis by inducing tolerance in both OVA-reactive and non-OVA-reactive T cells and by inducing Ag-nonspecific Treg cells. Such a mechanism might allow for Ag-nonspecific modulation of intestinal inflammation in inflammatory bowel disease.
authors.affiliation: Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhou
authors.forename: Rajka
authors.initials: R
authors.lastname: Borojevic
authors.forename: Cathy
authors.initials: C
authors.lastname: Streutker
authors.forename: Denis
authors.initials: D
authors.lastname: Snider
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Croitoru
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D018928:Immunity, Mucosal / Q000235:genetics; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D010047:Ovalbumin; D017493:Leukocyte Common Antigens