Self-reactive T cells induce and perpetuate chronic relapsing arthritis

Abstract

Background: 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. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsingremitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4 + T cells from lymph nodes of pristaneinjected 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. Conclusion: These 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.

Untitled

“…Phytol interacts with the nuclear factor kappa -B (NF-κB) signaling pathway and migration of neutrophils into inflammation sites that further causes the inhibition of pro-inflammatory cytokines such as TNF-α and interleukin -6, hence can regulate the inflammatory process of arthritis 25,28 .…”

Association BetweenAIREPolymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study

“…In vitro and in vivo studies have demonstrated that presentation of peripheral tissue self-antigens is quantitatively determined by AIRE transcription, and AIRE SNPs may cause clonal survival (19,47). Autoreactive CD4 + T cells are recruited to the synovium where they initiate an inflammatory environment by the production of interferon-gamma, tumor necrosis factor-alpha, interleukins (ILs), proinflammatory cytokines, and chemokines, causing tissue destruction (48)(49)(50). The inflammatory environment activates fibroblast-like synoviocytes (FLSs) to produce chemokines in order to attract more autoreactive CD4+ T cells, creating a vicious circle (50,51).…”

Difficult-to-treat rheumatoid arthritis treated with Abatacept combined with Baricitinib: A case report

“…Furthermore, from an immunogenetics standpoint, T-lymphocyte pathways play a significant role in inducing and perpetuating chronic relapsing arthritis of D2TRA[ 12 ]. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was first identified as an inhibitory signal that is delivered to stop the immune response and has the potential to adversely limit T-lymphocyte activation in various ways[ 13 ]. In several research investigations, the prevalence of D2T RA ranged from 5% to 20% of patients with RA[ 14 ].…”