Article

Valencia, X. et al. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J. Immunol. 178, 2579-2588

Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, MD 20892, USA.
The Journal of Immunology (Impact Factor: 4.92). 03/2007; 178(4):2579-88. DOI: 10.4049/jimmunol.178.4.2579
Source: PubMed

ABSTRACT

CD4(+)CD25(+) T regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance to nuclear components. We hypothesized that altered function of CD4(+)CD25(high) Tregs might play a role in the breakdown of immunologic self-tolerance in patients with SLE. In this study, we report a significant decrease in the suppressive function of CD4(+)CD25(high) Tregs from peripheral blood of patients with active SLE as compared with normal donors and patients with inactive SLE. Notably, CD4(+)CD25(high) Tregs isolated from patients with active SLE expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4(+) effector T cells in vitro. In contrast, the expression of FoxP3 mRNA and protein and in vitro suppression of the proliferation of CD4(+) effector T cells by Tregs isolated from inactive SLE patients, was comparable to that of normal individuals. In vitro activation of CD4(+)CD25(high) Tregs from patients with active SLE increased FoxP3 mRNA and protein expression and restored their suppressive function. These data are the first to demonstrate a reversible defect in CD4(+)CD25(high) Treg function in patients with active SLE, and suggest that strategies to enhance the function of these cells might benefit patients with this autoimmune disease.

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    • "CD4+ CD25+ Tregs were quantified with a flow cytometry method from whole blood samples collected into EDTA[21]. One hundred µl of samples were labeled 20min at room temperature with 10 µl PE-CD25, Phycoerythrin-Texas Red (ECD)-CD4, and Phycoerythrin- Cyanin5 (PC5)-CD3 antibodies (Beckman Coulter). "
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    • "Studies in SLE patients have reported conflicting data regarding the frequency, phenotype, and function of these cells. The heterogeneity in findings of decreased (7-13), normal, or even increased frequency of TREG cells in SLE (14-18) may be partially due to the criteria adopted in each study to define the TREG cell phenotype. We recently demonstrated that the CD25high gate, considered by some studies as characteristic for TREG cells, contains high levels of activated effector T cells in the active stages of SLE (4). "
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