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

Zhaohui Qian, Kary A. Latham, Karen B. Whittington, David C. Miller, David Brand, Edward F. Rosloniec

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)110-118
Number of pages9
JournalJournal of Immunology
Volume185
Issue number1
DOIs
StatePublished - Jul 1 2010

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HLA-DR1 Antigen
Autoantigens
Arthritis
Joints
T-Lymphocytes
T-Cell Antigen Receptor Specificity
Inflammation
Population
Experimental Arthritis
Collagen Type II
Hybridomas
Autoimmunity
Autoimmune Diseases

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joints of mice in an HLA-DR1 humanized mouse model of autoimmune arthritis. / Qian, Zhaohui; Latham, Kary A.; Whittington, Karen B.; Miller, David C.; Brand, David; Rosloniec, Edward F.

In: Journal of Immunology, Vol. 185, No. 1, 01.07.2010, p. 110-118.

Research output: Contribution to journalArticle

Qian, Zhaohui ; Latham, Kary A. ; Whittington, Karen B. ; Miller, David C. ; Brand, David ; Rosloniec, Edward F. / An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joints of mice in an HLA-DR1 humanized mouse model of autoimmune arthritis. In: Journal of Immunology. 2010 ; Vol. 185, No. 1. pp. 110-118.
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