Circulating Th17 and Th1 cells expressing CD161 are associated with disease activity in rheumatoid arthritis

Abstract

Objectives: To determine whether the percentages of major CD4+CD161+ T-cell subsets [T-helper (Th)17, Th1, and Th17/Th1] in peripheral blood are correlated with disease activity of rheumatoid arthritis (RA).

Method: In 42 RA patients and 15 healthy controls (HCs), the percentages of interleukin (IL)-17- and/or interferon (IFN)-γ-producing CD4+CD161+ T cells and the plasma levels of related cytokines were assessed by flow cytometry and cytometric bead array (CBA) analysis, respectively. Disease activity was evaluated by the 28-joint Disease Activity Score (DAS28).

Results: The percentage of circulating CD4+CD161+IL-17+IFN-γ− T cells (CD161+ Th17) in RA patients increased significantly and was higher in patients with active disease status (DAS28 > 3.2) compared with those with low disease status (DAS28 ≤ 3.2), and correlated positively with DAS28, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-17, and IL-6 levels in RA patients. The percentage of circulating CD4+CD161+IL-17−IFN-γ+ T cells (CD161+ Th1) decreased and correlated negatively with DAS28, CRP, and ESR levels in RA patients, while the percentage of CD4+CD161+IL-17+IFN-γ+ T cells (CD161+ Th17/Th1) was unchanged in RA patients and was not correlated with RA disease activity.

Conclusions: These data suggest that the percentages of circulating CD161+ Th17 and CD161+ Th1 cells in RA patients reflect the degree of disease activity. They support the hypothesis that Th17 cells are involved in the pathogenesis of RA and that CD161+ Th17/CD161+ Th1-cell imbalance may contribute to the development of RA.

Acknowledgements

This study was supported by grants from the Key Program of the National Natural Science Foundation of China (No. 81030058) and the National Science and Technology Major Project of China (No. 2012ZX09103301-026, 2013ZX09301-301).