Circulating T helper cells with T follicular helper cell phenotype renders the autoantibody generation in patients with systemic lupus erythematosus (HUM7P.304)

SLE is a chronic autoimmune disease characterized by autoreactive B cells and autoantibody production. Follicular helper T (Tfh) cells, a T cell subset located in the germinal center (GC) of lymphoid organs, is a key participant regulating B cell tolerance and antibody production. To identify the role of circulating Tfh (cTfh) cells in SLE, we examined their phenotype and function on supporting antibody production, and their correlation with autoantibody level and disease activity. Peripheral blood was collected from 29 SLE patients and age/gender-matched healthy donors. Tonsils from non-SLE controls were used to extract GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, and PD-1) via flow cytometry. IL-21 expression was measured by real-time PCR and intracellular staining. Tfh cells, non-Tfh cells were purified by MACS columns and co-cultured with B cells. IgG in the culture supernatant was detected by ELISA. Our results showed that cTfh cells in SLE patients expressed GC-Tfh signature molecules and IL-21 and were capable of driving B cells differentiate into plasma cells in vitro. The elevated frequency of cTfh cells correlated positively with levels of circulating plasmablasts, serum anti-dsDNA Ab and ANA. Our data suggests that the increased cTfh cells in SLE patients share phenotypic and functional properties with GC-Tfh cells. Tfh cells may serve as perpetrator to the pathogenesis in SLE patients and target for novel treatment.