Impaired Function of PD-1+ Follicular Regulatory T Cells in Systemic Lupus Erythematosus

Abstract Objective: Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE) but follicular regulatory T (TFR) cells potentially can suppress this abnormality. Here, we investigate functional changes in TFR cells from SLE patients. Methods: Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls to compare molecular expression and in vitro suppressive capacity of follicular helper T (TFH) cell proliferation. We then tested IL-2 in SLE-TFR cells to check restoration of suppressor function. Results: Programmed death-1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators forkhead box p3 (Foxp3), cytotoxic T-lymphocyte antigen 4 (CTLA4), and IL-2 receptor alpha (IL2Rα). In vitro IL-2 stimulation restored expression of these molecules. Conclusion: SLE-TFR cells have functional TFH suppression defects but low-dose IL-2 therapy could be useful to restore this ability.