Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus.
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.
Valencia
Xavier
X
Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, MD 20892, USA. xvalencia@mail.nih.gov
Yarboro
Cheryl
C
Illei
Gabor
G
Lipsky
Peter E
PE
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors