OBJECTIVE: The increment of CD4CD25Foxp3T 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 CD4CD25Foxp3T cells and Treg cells (CD4CD25Foxp3 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 CD4CD25Foxp3 T cells and Treg cells were performed by flow cytometry. The correlation of CD4CD25Foxp3T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. RESULTS: CD4CD25Foxp3 T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4CD25Foxp3 T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4CD25Foxp3 T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4CD25Foxp3 T cells expressed more IFN-γ and less CTLA-4 than CD4CD25Foxp3 T cells, which were similar to CD4CD25Foxp3 T cells, and expressed similar IL-17, ICOS and Helios to CD4CD25Foxp3 T cells. The synthesis capacity of IL-10 of CD4CD25Foxp3 T cells and the expression of GITR on CD4CD25Foxp3 T cells were between CD4CD25Foxp3 and CD4CD25Foxp3 T cells. CONCLUSIONS: Our results indicate that increased CD4CD25Foxp3 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.