Of mice and men: how animal models advance our understanding of T-cell function in RA

Nat Rev Rheumatol. 2014 Mar;10(3):160-70. doi: 10.1038/nrrheum.2013.205. Epub 2014 Jan 7.

Abstract

The involvement of autoreactive T cells in the pathogenesis of rheumatoid arthritis (RA) as well as in autoimmune animal models of arthritis has been well established; however, unanswered questions, such as the role of joint-homing T cells, remain. Animal models of arthritis are superb experimental tools in demonstrating how T cells trigger joint inflammation, and thus can help to further our knowledge of disease mechanisms and potential therapies. In this Review, we discuss the similarities and differences in T-cell subsets and functions between RA and mouse arthritis models. For example, various T-cell subsets are involved in both human and mouse arthritis, but differences might exist in the cytokine regulation and plasticity of these cells. With regard to joint-homing T cells, an abundance of synovial T cells is present in humans compared with mice. On the other hand, local expansion of type 17 T-helper (TH17) cells is observed in some animal models, but not in RA. Finally, whereas T-cell depletion therapy essentially failed in RA, antibody targeting of T cells can work, at least preventatively, in most arthritis models. Clearly, additional human and animal studies are needed to fill the gap in our understanding of the specific contribution of T-cell subsets to arthritis in mice and men.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology*
  • Biological Factors / therapeutic use
  • Cytokines / physiology
  • Disease Models, Animal*
  • Humans
  • Mice
  • T-Lymphocytes / physiology*
  • Th17 Cells / physiology

Substances

  • Biological Factors
  • Cytokines