title: Colitis-related public T cells are selected in the colonic lamina propria of IL-10-deficient mice.
abstract: IL-10 is an important regulatory cytokine in the mucosal immune system, as supported by the fact that mice deficient in IL-10 spontaneously develop Crohn's disease-like colitis. An aberrant, Th1-driven CD4(+) T-cell response to enteric bacteria seems to be important in the pathogenesis of this murine colitis. However, no specific bacteria or bacterial products have been identified, and whether the colitis is mediated by the activation of CD4(+) T cells that recognize specific peptide-MHC complexes is controversial. In this study, we analyzed the TCR beta chain complementarity determining region 3 length spectratype of colonic CD4(+) T cells isolated from diseased IL-10-deficient mice by using the Immunoscope technique. Screening of the diseased interleukin-10-deficient mice resulted in a restricted clonotype in TCR V beta 13 and 14 subfamilies of colonic CD4(+) T cells. In contrast, a Gaussian distribution of clonotype of individual TCR V beta subsets was observed in CD4(+) T cells from the peripheral lymphoid tissues. Although individual variability in the disease-related response was also noted in other IL-10-deficient mice maintained in La Jolla and Osaka, perhaps because of different stages of the disease, genetic background, or the housing environment, colitis-related public clones seemed to be shared in all the diseased mice tested. To address whether public clones were involved, we determined the DNA sequence of the clones. Public motifs were shared in colonic CD4(+) T cells from different background interleukin-10-deficient mice with colitis. The frequently found motifs were SXDWG and SATGNYAEQ. These motifs were not seen in the peripheral lymphoid tissues of diseased mice as well as the colon of non-diseased mice. Thus, the common motif may be related to a public gut-derived antigen, which could be important for the development of pathogenic CD4(+) T cells in this inflammatory bowel disease (IBD) model. The selection of V beta-J beta usage is perhaps stochastic in individual mice; however, the epigenetic generation of SXDWG motif by the recombination machinery and selection for this motif in the gut environment could be important for triggering IBD.
authors.affiliation: Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takahashi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Matsuda
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.forename: Hilde
authors.initials: H
authors.lastname: DeWinter
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamagawa
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D019976:Cloning, Organism; D003092:Colitis / Q000276:immunology* / Q000382:microbiology; D003106:Colon / Q000276:immunology* / Q000382:microbiology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016753:Interleukin-10