Self-reactive T cells induce and perpetuate chronic relapsing arthritis

Jonatan Tuncel,Rikard Holmdahl,Sabrina Haag,Stefan Carlsen,Jens Holmberg,Malin Hultqvist Hopkins,Peter Olofsson,Lena Wester-Rosenlöf

doi:10.1186/s13075-020-2104-7

Jonatan Tuncel, Rikard Holmdahl + Show 6 more

Open Access

https://doi.org/10.1186/s13075-020-2104-7

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Abstract

BackgroundCD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis.MethodsWe used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis.ResultsRats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission.ConclusionThese findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.

Highlights

Rheumatoid arthritis (RA) is a chronic relapsing autoimmune disease that affects approximately 0.5% of the population
CD4+ T cells from lymph nodes, but not spleen, transfer chronic arthritis In contrast to the high incidence of chronic arthritis in rats injected with pristane [17], the disease induced by the adoptive transfer of spleen-derived T cells from pristaneinjected rats is acute and resolves spontaneously after 4–5
Following an almost complete remission, the arthritis relapsed in rats transferred with Lymph node (LN)-derived, but not spleenderived, T cells (Fig. 1a, b), and the histological examination at the end of the experiment demonstrated that several, albeit not all, of the rats transferred with LNderived T cells had joints with severe pannus formation (Fig. 1c)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic relapsing autoimmune disease that affects approximately 0.5% of the population. Several lines of evidence indicate that CD4+ αβ T cells play a central role in the disease. While there is a broad consensus that T cells are important in RA, it is still unclear what role they play during the various stages of the disease [8]. Self- or crossreactive T cells may contribute at an early stage of RA by providing co-stimulation to B cells to promote the production of autoantibodies. CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis

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