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

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.

Figure 1

Cytokine regulation of the T_H17–T_REG cell axis in human RA and its mouse models. Naive T cells can differentiate into either T_H17 or T_REG cells and there is high plasticity between these T cell subsets. This figure summarizes inflammatory mediators enabling the differentiation of these T-cell subsets, and those mediators produced by these cells in humans and mice. Similarities and differences between human and mouse arthritis with respect to T-cell subsets are further explained in the main text and in Table 1. Abbreviations: CCR, CC-chemokine receptor; FOXP3, forkhead box P3; RA, rheumatoid arthritis; ROR, retinoic acid receptor-related orphan receptor; STAT, signal transducer and activator of transcription; TGF-β, transforming growth factor β; T_REG, regulatory T; T_H, T helper.