Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement. (November 2018) - Yin, Z-J
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.