Significant association of CD4+CD25+Foxp3+ regulatory T cells with clinical findings in patients with systemic lupus erythematosus.

Abstract

Regulatory T (Treg) cells are one of the important mechanisms in maintaining self-tolerance and immune homeostasis. CD4+CD25+Foxp3+Treg is considered to have a role in the pathogenesis of systemic lupus erythematosus (SLE). However, the data reported is controversial, and a conclusive result has not been given thus far. The aim of the present study is to evaluate the role of CD4+Treg in SLE further. The peripheral blood T cells (PBMCs) from patients with SLE and healthy controls were isolated, and followed by the isolation of CD3+T cells. The PBMCs were tested for the expressions of CD25 and Foxp3 molecules on the surface of CD4+T cells, and CD3+T cells were tested for their cytokine expressions including IFN-γ, TGF-β, and IL-10, with the method of flow cytometry. The correlations of test results with clinical features of the disease were evaluated by linear correlation analysis. CD4+CD25+ Foxp3+Treg decreased in SLE patients and was correlated with the SLE Disease Activity Index (SLEDAI), and a few immunological abnormalities, including anti-dsDNA antibody positive, IgG increase and C3 decrease, and types of tissue damage, including leukocytopenia and kidney damage. IFN-γ+ cells in the CD4+CD25+T subset fresh-isolated from SLE patients increased slightly, but IFN-γ-producing response to stimulation in CD4+CD25+T subset of SLE decreased. The number of TGF-β-producing cells in the CD4+CD25+T subset from SLE patients also decreased. While the percentages of CD4+CD25+IL-10+T subset in the CD3+T cells increased in SLE, however, these changes of cytokine expressions did not show any significant correlations with SLEDAI. There is clear and definite evidence from the present study indicating the important role of CD4+CD25+Foxp3+Treg in the pathogenesis of SLE, for the abnormalities in functional cytokine productions of the CD4+CD25+ T subset, and for the feasibility of a CD4+CD25+Foxp3+Treg- based immunotherapy in SLE.