Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus

J Immunol. 2007 Feb 15;178(4):2579-88. doi: 10.4049/jimmunol.178.4.2579.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Cell Proliferation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology*
  • Gene Expression Regulation / immunology*
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / pathology
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Self Tolerance*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology


  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors