CD70-expressing CD4 T cells produce IFN-γ and IL-17 in rheumatoid arthritis

Objective. CD70-expressing CD4 T cells are enriched in RA and promote autoimmunity via co-stimulatory CD70-CD27 interaction. This study aimed to explore the phenotype and cytokine production of CD70+ CD4 T cells in RA. Methods. Peripheral blood mononuclear cells from 32 RA patients were isolated and frequencies of CD70+ cells within different CD4 T subsets were analysed using flow cytometry. IFN-γ and IL-17 production were compared between the CD70+ and CD70− cells. Expression of master transcription factors T-bet, GATA3 and retinoic acid–related orphan receptor gamma t (RORγt) were examined by real-time PCR. Results are presented as mean (s.e.m.). Results. CD4 T cells of healthy controls rarely expressed CD70 as compared with CD4 T cells of RA patients [mean 0.9% (s.e.m. 0.3%) vs 7.6 (0.6), P < 0.001]. In RA, CD70+ cells were present within all CD4 T cell subsets, i.e. CD45RA+CCR7+ naive, CD45RA−CCR7+ central memory, CD45RA−CCR7− effector memory and CD45RA+CCR7− terminally differentiated effector memory T cells with a mean frequency of 3.9% (s.e.m. 1.1%), 4.0 (0.5), 4.2 (0.7) and 9.4 (4.3), respectively. As compared to CD70− CD4 T cells, CD70+ CD4 T cells produced significantly more IFN-γ and IL-17 after short activation. CD70+ CD4 T cells preferentially expressed transcription factor RORγt. Conclusion. CD70+ CD4 T cells are enriched in RA and may directly contribute to RA pathogenesis by producing IFN-γ and IL-17. Targeting CD70+ CD4 T cells might offer new therapeutic opportunities in RA.