Effects of steroids on circulating follicular helper T cell-like CD4+ T cells in patients with systemic lupus erythematosus

Abstract

Objective To analyze changes in the percentages of circulating follicular helper T (Tfh) cells and Tfh subsets in patients with systemic lupus erythematosus (SLE) for better understanding their relationships with SLE, and to investigate effects of steroids on circulating Tfh cells. Methods Peripheral blood mononuclear cells (PBMCs) from 27 patients with SLE (including 10 inactive patients and 17 active patients) and 21 sex- and age-matched healthy donors were analyzed by flow cytometry to detect the percentage of CD4+ CD45RA-CXCR5+ Tfh-like cells. Disease activity and the concentration of anti-double-stranded DNA (anti-dsDNA) antibody were evaluated by SLEDAI score (SLE disease activity index) and ELISA, respectively. PBMCs from healthy donors were treated with or without prednisone to evaluate its effects on circulating Tfh cells. Twelve patients with SLE were treated with high-dose steriods (200-500 mg/d, 2-3 d) and the percentages of circulating Tfh cells and Tfh subsets in them were analyzed before and after treatment. Results No significant difference in the percentage of circulating Tfh cells was observed between patients with SLE and healthy donors (P>0.05), but the percentage of Tfh17 cells in patients with SLE was significantly higher than that in healthy donors (P<0.05). Compared with patients with inactive SLE and healthy donors, patients with active SLE had a lower percentage of Tfh1 cells (P<0.05). Moreover, the percentage of Tfh1 cells was negatively correlated with SLEDAI score (r=-0.44, P<0.05). The percentage of Tfh2 cells in anti-dsDNA antibody-positive group was significantly higher than that in anti-dsDNA antibody-negative group (P<0.05). In vitro treatment of PBMCs from healthy donors with prednisone could significantly down-regulate the percentage of circulating Tfh (P<0.01), Tfh1 (P<0.05) and Tfh2 cells (P<0.01), and up-regulate the percentage of Tfh17 cells (P<0.01). In vivo treatment of patients with SLE with steriods could significantly down-regulate the percentage of circulating Tfh (P<0.01), Tfh1 (P<0.05) and Tfh2 cells (P<0.01) and up-regulate the percentage of Tfh17 cells (P<0.01). Conclusion Abnormal distribution of Tfh subsets is correlated with SLE disease activity and anti-dsDNA antibody. Steroids in the treatment of SLE could affect the percentage of circulating Tfh cells and the distribution of Tfh subsets. Key words: Systemic lupus erythematosus; Follicular helper T cell; Prednisone