title: Dysregulated luminal bacterial antigen-specific T-cell responses and antigen-presenting cell function in HLA-B27 transgenic rats with chronic colitis.
abstract: HLA-B27/beta2 microglobulin transgenic (TG) rats spontaneously develop T-cell-mediated colitis when colonized with normal commensal bacteria, but remain disease-free under germ-free conditions. We investigated regulation of in vitro T-cell responses to enteric bacterial components. Bacterial lysates prepared from the caecal contents of specific pathogen-free (SPF) rats stimulated interferon-gamma (IFN-gamma) production by TG but not non-TG mesenteric lymph node (MLN) cells. In contrast, essentially equivalent amounts of interleukin-10 (IL-10) were produced by TG and non-TG cells. However, when cells from MLNs of non-TG rats were cocultured with TG MLN cells, no suppression of IFN-gamma production was noted. Both non-TG and TG antigen-presenting cells (APC) pulsed with caecal bacterial lysate were able to induce IFN-gamma production by TG CD4+ cells, although non-TG APC were more efficient than TG APC. Interestingly, the addition of exogenous IL-10 inhibited non-TG APC but not TG APC stimulation of IFN-gamma production by cocultured TG CD4+ lymphocytes. Conversely, in the presence of exogenous IFN-gamma, production of IL-10 was significantly lower in the supernatants of TG compared to non-TG APC cultures. We conclude that commensal luminal bacterial components induce exaggerated in vitro IFN-gamma responses in HLA-B27 TG T cells, which may in turn inhibit the production of regulatory molecules, such as IL-10. Alterations in the production of IFN-gamma, and in responses to this cytokine, as well as possible resistance of TG cells to suppressive regulation could together contribute to the development of chronic colitis in TG rats.
authors.affiliation: Center for Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Qian
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tonkonogy
authors.forename: Frank
authors.initials: F
authors.lastname: Hoentjen
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005856:Germ-Free Life; D015796:HLA-B27 Antigen / Q000032:analysis* / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D015796:HLA-B27 Antigen; D016753:Interleukin-10; D007371:Interferon-gamma