DRB1*0402 may influence arthritis by promoting naive CD4+ T-cell differentiation in to regulatory T cells

David Luckey, Marshall Behrens, Michele Smart, Harvinder Luthra, Chella S. David, Veena Taneja

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

HLA-DRB1*0401 expression in humans has been associated with a predisposition to developing rheumatoid arthritis (RA) and collagen-induced arthritis (CIA), while HLA-DRB1*0402 is not associated with susceptibility. Here, we determined if mice transgenic (Tg) for human *0401 have a CD4+ T-cell repertoire that predetermines proinflammatory cytokine production. The data show that both *0401 and *0402 Tg mice can produce TH1/TH17 cytokines, although the kinetics of response may be different. However, in the context of antigen-specific responses in a CIA model, *0402 Tg mice generate a TH2 response that may explain their resistance to developing arthritis. In addition, a significant subset of naïve CD4+ T cells from *0402 Tg mice can be activated in polarizing conditions to differentiate into Treg cells that produce IFN-γ. *0401 Tg mice harbor memory CD4+ T cells that differentiate into IL-17+ cells in various polarizing conditions. Our data suggest that *0401 Tg mice generate a strong immune response to lipopolysaccharide and may be efficient in clearing infection, and may *0401 have been evolutionarily selected for this ability. Autoimmunity, such as RA, could likely be a bystander effect of the cytokine storm that, along with the presence of low Treg-cell numbers in *0401 Tg mice, causes immune dysregulation.

Original languageEnglish (US)
Pages (from-to)3429-3438
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Humanized mice
  • Immune dysregulation
  • Regulatory T cells
  • Rheumatoid arthritis
  • T-cell polarization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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