Elevated circulating T cell subsets and cytokines expression in patients with rheumatoid arthritis

Abstract

Objective: This study aimed to assess the role of different subsets of circulating follicular helper T cells (Tfh), central memory (TCM), effector memory (TEM), Naïve T, chemokines, and cytokines in the pathogenesis of rheumatoid arthritis (RA).

Methods: Blood samples from RA patients (n = 44) and healthy controls (n = 37) were analyzed. The frequencies of circulating Tfh, TCM, TEM, and Naïve T cell subsets were enumerated, and the expression of co-stimulatory molecules, such as inducible co-stimulator (ICOS) and programmed death-1 (PD1), on these cells was evaluated by flow cytometry. The disease state in RA patients was assessed using the DAS28. Concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were measured. Cytokines and chemokines, such as IL-1β, TNF-α, IL-4, IL-6, IL-9, IL-17A, MCP-1, IL-10, IL-12p70, and IL-21, were measured by a cytometric beads array assay.

Results: The percentages of circulating PD1⁺ICOS⁺ Tfh, PD1⁺ICOS⁺ TEM, and PD1⁺ICOS⁺ TCM of PBMCs from RA patients were higher than those in healthy controls. Furthermore, expression of circulating PD1⁺ICOS⁺ Tfh, PD1⁺ICOS⁺ TEM, and PD1⁺ICOS⁺ TCM showed a positive correlation with DAS28. In addition, increased levels of IL-1β, IL-6, and MCP-1 were detected in the patients with RA compared to healthy controls.

Conclusions: Elevated circulating T cell subsets and cytokines expression profile were observed in RA patients. IL-6, MCP-1, and IL-1β were significantly increased in RA, and PD1⁺ICOS⁺ TEM, PD1⁺ICOS⁺ TCM, and PD1⁺ICOS⁺ Tfh cell subsets were positively correlated with disease activity DAS28. Therefore, PD1⁺ICOS⁺ TEM, PD1⁺ICOS⁺ TCM, and PD1⁺ICOS⁺ Tfh cells might serve an important role in the progression of RA.

Keywords: Follicular help T cells; Memory T cells; Rheumatoid arthritis.