An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joints of mice in an HLA-DR1 humanized mouse model of autoimmune arthritis

J Immunol. 2010 Jul 1;185(1):110-8. doi: 10.4049/jimmunol.1000416. Epub 2010 May 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Cattle
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Clone Cells
  • Collagen Type II / genetics
  • Collagen Type II / immunology*
  • HLA-A Antigens / biosynthesis
  • HLA-A Antigens / genetics
  • HLA-DR1 Antigen / biosynthesis
  • HLA-DR1 Antigen / genetics
  • HLA-DR1 Antigen / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Severity of Illness Index
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*

Substances

  • Autoantigens
  • Collagen Type II
  • HLA-A Antigens
  • HLA-DR1 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*01:01 antigen
  • Receptors, Antigen, T-Cell, alpha-beta