An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joints of mice in an HLA-DR1 humanized mouse model of autoimmune arthritis.
Although it is clear that CD4(+) T cells play a major role in mediating the pathogenesis of autoimmunity, they often represent only a minor population at the site of inflammation in autoimmune diseases. To investigate the migration and specificity of autoimmune T cells to the inflammatory site, we used the collagen-induced arthritis model to determine the frequency, clonotype, and specificity of T cells that infiltrate arthritic joints. We demonstrate that despite the fact that CD4(+) T cells are a minor population of the synovial infiltrate, the CD4(+) T cells present are a highly selective subset of the TCR repertoire and, based on CDR3 length polymorphisms, have a limited clonality. Although a similar repertoire of type II collagen (CII)-specific TCR-BV8 and BV14-expressing T cells was found in peripheral lymphoid organs, the clonality of the TCR-BV8 and BV14 T cells that migrate to the arthritic joint generally made up a single CDR3 length. T cell hybridomas produced from these joint-derived cells revealed that many of these infiltrating T cells are CII specific, and the majority recognize mouse CII. These data suggest that despite being a minor population at the site of inflammation, autoantigen-specific T cells are selectively recruited and/or retained in the arthritic joint and may be playing a significant role in the pathogenesis of the autoimmune arthritis. In addition, this model may be very useful for studying the function in situ and the mechanism by which autoimmune T cells are recruited to the site of inflammation.
Veterans Affairs Medical Center, Memphis, TN 38104, USA.
Zhaohui
Z
Qian
Kary A
KA
Latham
Karen B
KB
Whittington
David C
DC
Miller
David D
DD
Brand
Edward F
EF
Rosloniec
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D024043:Collagen Type II / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D001324:Autoantigens; D024043:Collagen Type II; D015234:HLA-A Antigens; D015798:HLA-DR1 Antigen; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta