Increased CD4 + CD25 - Foxp3 + T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Abstract

Objective

The increment of CD4⁺CD25⁻Foxp3⁺T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4⁺CD25⁻Foxp3⁺T cells and Treg cells (CD4⁺CD25⁺Foxp3⁺ T cells) in a large sample of Chinese SLE patients in different disease states.

Methods

A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4⁺CD25⁻Foxp3⁺ T cells and Treg cells were performed by flow cytometry. The correlation of CD4⁺CD25⁻Foxp3⁺T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed.

Results

CD4⁺CD25⁻Foxp3⁺ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4⁺CD25⁻Foxp3⁺ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4⁺CD25⁻Foxp3⁺ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4⁺CD25⁻Foxp3⁺ T cells expressed more IFN-γ and less CTLA-4 than CD4⁺CD25⁺Foxp3⁺ T cells, which were similar to CD4⁺CD25⁺Foxp3⁻ T cells, and expressed similar IL-17, ICOS and Helios to CD4⁺CD25⁺Foxp3⁺ T cells. The synthesis capacity of IL-10 of CD4⁺CD25⁻Foxp3⁺ T cells and the expression of GITR on CD4⁺CD25⁻Foxp3⁺ T cells were between CD4⁺CD25⁺Foxp3⁺ and CD4⁺CD25⁺Foxp3⁻ T cells.

Conclusions

Our results indicate that increased CD4⁺CD25⁻Foxp3⁺ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.