Reduction of forkhead box P3 levels in CD4+CD25high T cells in patients with new-onset systemic lupus erythematosus

Abstract

The aim of this study was to quantify and evaluate the forkhead box P3 (FoxP3) expression regulatory T cells in new-onset systemic lupus erythematosus (SLE) patients before and after treatment. Forty-four newly diagnosed and untreated SLE patients, including 24 with active disease (SLEDAI > or = 10) and 20 with inactive disease (SLEDAI < 5), were enrolled in this study. Twenty-one age- and sex-matched healthy volunteers were also included as controls. Peripheral blood samples were collected and mononuclear cells isolated. The expression of CD25 and FoxP3 in CD4(+) T cells were analysed with flow cytometry. CD4(+)CD25(+) (3.95-13.04%) and CD4(+)CD25(high) (0.04-1.34%) T cells in peripheral blood in untreated patients with new-onset active lupus were significantly lower than that in the patients with inactive lupus (7.27-24.48%, P < 0.05 and 0.14-3.07% P < 0.01 respectively) and that in healthy controls (5.84-14.84%, P < 0.05). Interestingly, the decrease in CD4(+)CD25(high) T cells was restored significantly in patients with active lupus after corticosteroid treatment. There was, however, a significantly higher percentage of CD4(+)FoxP3(+) T cells in patients with active (5.30-23.00%) and inactive (7.46-17.38%) new-onset lupus patients compared with healthy control subjects (2.51-12.94%) (P < 0.01). Intriguingly, CD25 expression in CD4(+)FoxP3(+) T cells in patients with active lupus (25.24-62.47%) was significantly lower than that in those patients with inactive lupus (30.35-75.25%, P < 0.05) and healthy controls (54.83-86.38%, P < 0.01). Most strikingly, the levels of FoxP3 expression determined by mean fluorescence intensity in CD4(+)CD25(high) cells in patients with active SLE were significantly down-regulated compared with healthy subjects (130 +/- 22 versus 162 +/- 21, P = 0.012). CD4(+)CD25(high) T cells are low in new-onset patients with active SLE and restored after treatment. Despite that the percentage of CD4(+)FoxP3(+) T cells appear high, the levels of FoxP3 expression in CD4(+)CD25(high) T cells are down-regulated in untreated lupus patients. There is a disproportional expression between CD25(high) and FoxP3(+) in new-onset patients with active SLE.