Background/Purpose: T follicular helper (Tfh) cells are a new subset of T helper cells that regulate B cell function and promote autoantibody production. We previously reported that T helper cell differentiation exhibits Tfh-like transitional stage which is regulated by dynamic balance of transcription factors. However, the role of this subset in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The purpose of this study was to assess the characteristic and pathological role of Tfh cells in patients with RA.

Methods: Peripheral blood mononuclear cell (PBMC) was obtained from patients with 49 RA and 35 other autoimmune diseases including systemic lupus erythematosus (SLE) and Sjogren’s syndrome (SS), as well as from 10 healthy donors (HD). PBMCs were analyzed by 8 color staining multiparameter flow cytometry. The proportion of T cell subsets was determined by expression of chemokine receptors and the results were correlated with patient characteristics, including the titer of autoantibodies (RF, ACPA), CRP, ESR, MMP-3 and simplified disease activity index (SDAI).

Results: The number of effector memory T cells has increased in RA patients compared with HD. The proportion of CD4⁺CXCR3⁺ Th1 cells, CD4⁺CCR6⁺ Th17 cells, and CD4⁺CXCR5⁺ Tfh cells was not different among HD, RA, and other autoimmune diseases including SLE and SS. The frequency of activated Tfh cells was significantly correlated with the presence of ACPA in RA patients. The proportion of the CD4⁺CXCR3⁺CXCR5⁺ (Th1/Tfh) cells and CD4⁺CCR6⁺CXCR5⁺ (Th17/Tfh) cells was increased in patients with RA and SLE compared to HD. We found that the sub-population of Tfh cells which express intermediate levels of CXCR5, CXCR3 and CCR6 all together has characteristically increased in patients with RA compared to both HD and other autoimmune diseases. Those cells also expressed surface activation markers such as CD38 and CD69. The frequency of those cells was closely correlated with CRP, ESR, MMP-3, and SDAI, whereas those of Th1 cells and Th17 cells showed no correlation.

Conclusion: The new population of T helper cells, which shares triple phenotypes of Th1/Th17/Tfh (transitional Tfh like: tTfh) cells, was identified. These findings have shown that the increased frequency of tTfh cells is correlated with disease activity of RA, indicating the possible involvement of tTfh cells in the disease progression of RA. Our findings also provided the concept that Tfh cells are most plastic and flexible T helper subsets in human and support the relevance of tTfh cells as a potential therapeutic target for RA.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/involvement-of-transitional-t-follicular-like-helper-cells-bearing-triple-phenotypes-of-tfhth1th17-in-the-pathogenesis-of-rheumatoid-arthritis/