Abatacept therapy reduces CD28+CXCR5+ follicular helper-like T cells in patients with rheumatoid arthritis.

OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT.

METHODS: We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated.

RESULTS: RA patients showed an increase in the proportion of CD28- cells among CD4+ cells, which was significantly high in patients who had not achieved remission after ABT therapy. The proportions of CD4+CXCR5+ T follicular helper-like (Tfh-like) cells increased in RA patients compared to healthy donors. The proportions of Tfh-like cells among CD4+CD28+ cells were significantly higher than those among CD4+CD28- cells. The proportion of Tfh-like cells was higher in anti-cyclic citrullinated peptide antibody (ACPA)-positive patients. By contrast, the proportions of CD4+CXCR3+ T helper 1-like (Th1-like) cells and effector memory phase T cells among CD4+CD28- cells were significantly higher than those among CD4+CD28+ cells, and the proportion of these cells did not correlate with disease activity. After ABT therapy, the proportion of Tfh-like cells among CD4+CD28+ cells was significantly reduced.

CONCLUSIONS: These results imply that CD4+ CD28+ Tfh-like cells could possibly be the targets of ABT. Conversely, CD4+ CD28- cells may be a potential predictor of treatment resistance.