Article Abstract

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

Authors: Xiaofan Yang, Weiwen Wang, Juan Xu, Ming-Shun Zhang, Huanping Mei, Youxuan Shen, Miao-Jia Zhang, Xiaohui Ji, Huijuan Wang


Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.