Clonal expansion of CD4+ TCRbetabeta+ T cells in TCR alpha-chain- deficient mice by gut-derived antigens.
A population of CD4+ alpha-beta+ T cells increases in the mucosal and peripheral lymphoid tissues of TCRalpha-chain-deficient mice with inflammatory bowel disease. The alpha-beta+ T cells, which produce predominantly IL-4, mediate the proliferation of colonic epithelial crypts and the infiltration of large numbers of IgA-producing plasma cells into the lamina propria of the colon. To examine whether enteric Ags were recognized by a population of monoclonal alpha-beta+ T cells leading to the intestinal inflammation, we examined the usage and clonotypes of TCR expressed by the alpha-beta+ T cells in TCRalpha-chain-deficient mice with inflammatory bowel disease. Analyses of immunoprecipitates by two dimensional electrophoresis and single-cell RT-PCR revealed that TCR of the alpha-beta+ T cells was a homodimer of beta-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR Vbeta transcripts revealed monoclonal accumulation of the alpha-beta+ T cells in the colonic lamina propria of the diseased mice. DNA sequencing revealed the accumulation of the alpha-beta+ T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4+ alpha-beta+ T cells expressing a homodimeric form of the TCRbeta-chains can be clonally expanded upon the stimulation with gut-derived Ags.
Takahashi
I
I
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Iijima
H
H
Katashima
R
R
Itakura
M
M
Kiyono
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D004247:DNA / Q000235:genetics; D004064:Digestive System / Q000276:immunology*; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction