Systemic lupus erythematosus exhibits a dynamic and continuum spectrum of effector/regulatory T cells

Abstract

OBJECTIVE: The identification of regulatory T cells (Treg cells) as CD4(+)CD25(high) cells may be upset by the increased frequency of activated effector T cells (Teff cells) in inflammatory diseases such as systemic lupus erythematosus (SLE). This study aimed to evaluate the frequency of T-cell subsets according to the expression of CD25 and CD127 in active (A-SLE) and inactive SLE (I-SLE). METHODS: Peripheral blood mononuclear cells (PBMCs) from 26 A-SLE patients (SLE Disease Activity Index (SLEDAI) = 10.17 ± 3.7), 31 I-SLE patients (SLEDAI = 0), and 26 healthy controls (HC) were analysed by multicolour flow cytometry. RESULTS: CD25(high) cell frequency was increased in A-SLE (5.2 ± 5.7%) compared to I-SLE (3.4 ± 3.4%) and HC (1.73 ± 0.8%) (p < 0.01). However, the percentage of FoxP3(+) cells in the CD25(high) subset was decreased in A-SLE (24.6 ± 16.4%) compared to I-SLE (33.7 ± 16) and HC (45 ± 25.1%) (p < 0.01). This was partly due to the increased frequency of Teff cells (CD25(high)CD127(+)FoxP3(Ø)) in A-SLE (10.7 ± 7.3%) compared to I-SLE (8.5 ± 6.5) and HC (6.1 ± 1.8%) (p = 0.02). Hence the frequency of Treg cells (CD25(+/high)CD127(low/Ø)FoxP3(+)) was equivalent in A-SLE (1.4 ± 0.8%), I-SLE (1.37 ± 1.0%), and HC (1.13 ± 0.59%) (p = 0.42). A-SLE presented an increased frequency of CD25(+)CD127(+)FoxP3(+) and CD25(Ø)FoxP3(+)CD127(low/Ø) T cells, which may represent intermediate phenotypes between Treg and Teff cells. CONCLUSIONS: The present study has provided data supporting normal Treg cell frequency in A-SLE and I-SLE as well as increased frequency of Teff cells in A-SLE. This scenario reflects a Treg/Teff ratio imbalance that may favour the inflammatory phenotype of the disease. In addition, the increased frequency of T cells with putative intermediate phenotypes may be compatible with a highly dynamic immune system in SLE.