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

Nature Reviews Rheumatology volume 10, pages 160–170 (2014)Cite this article

Subjects

Key Points

  • Autoreactive T cells have an important role in the pathogenesis of both rheumatoid arthritis (RA) and mouse models of the disease

  • In addition to similarities, some differences exist in the regulation of the development and plasticity of type 1 and type 17 T-helper cell and regulatory T-cell subsets in humans and mice

  • The contribution of joint-homing T cells to local inflammation in arthritis is not clear in either species

  • Unlike in mouse arthritis, most T-cell-targeting therapeutic strategies failed in RA; only a few of them (such as abatacept) succeeded

  • Anti-cytokine and anti-B-cell therapies might indirectly suppress pathogenic T cells in human and mouse arthritis

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.

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Figure 1: Cytokine regulation of the TH17–TREG cell axis in human RA and its mouse models.

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Acknowledgements

Z. Szekanecz is supported by the Medical Research Council of Hungary research grant ETT 315/2009 and by the European Union, European Social Fund and Hungary co-financed projects TÁMOP 4.2.1/B-09/1/KONV-2010-0007 and TÁMOP-4.2.2.A-11/1/KONV-2012-0031 National Excellence Convergence Program. T. T. Glant is supported by NIH grant R01 AR059356. K. Mikecz is supported by NIH grants R01 AR064206 and R21 AR062332.

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Authors and Affiliations

  1. Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Science Centre, 98 Nagyerdei Street, Debrecen, H-4032, Hungary

    Tamás Kobezda, Sheida Ghassemi-Nejad & Zoltán Szekanecz

  2. Departments of Orthopedic Surgery, Section of Molecular Medicine, Biochemistry and Rheumatology, Rush University Medical Centre, 1735 West Harrison Street, Chicago, 60612, IL, USA

    Katalin Mikecz & Tibor T. Glant

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  1. Tamás Kobezda
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  2. Sheida Ghassemi-Nejad
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  3. Katalin Mikecz
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  4. Tibor T. Glant
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  5. Zoltán Szekanecz
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Contributions

All authors made substantial contributions to researching data for the article and writing the manuscript. In addition, K. Mikecz, T. T. Glant and Z. Szekanecz contributed to discussions of the content of the article, and T. Kobezda, K. Mikecz, T. T. Glant and Z. Szekanecz reviewed/edited the manuscript before submission.

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Correspondence to Zoltán Szekanecz.

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Kobezda, T., Ghassemi-Nejad, S., Mikecz, K. et al. Of mice and men: how animal models advance our understanding of T-cell function in RA. Nat Rev Rheumatol 10, 160–170 (2014). https://doi.org/10.1038/nrrheum.2013.205

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