CD4+CD25+ regulatory T cells (Treg) that specialize in the suppression of immune responses play a critical role in the regulation of peripheral immune tolerance and thus might be critically involved in the pathogenesis of autoimmune diseases. As for systemic lupus erythematosus (SLE), however, data concerning Treg are so far limited. We therefore initiated detailed quantitative and qualitative analysis of naturally occurring CD4+CD25+ Treg from SLE patients as compared with healthy controls. FACS analysis revealed increased proportions of CD4+CD25+ Treg, as well as activated CD4+CD69+ T cells, among peripheral blood mononuclear cells in SLE patients as compared with healthy controls. Ongoing experiments aim to analyze the capacity of purified CD4+CD25+ Treg to suppress the proliferation of autologous or allogeneic T cells. Preliminary results indicate a tendency towards a reduced suppressive capacity of CD4+CD25+ Treg in SLE patients as compared with healthy controls. Additional experiments will determine the statistical significance of this observation and will correlate quantitative and/or qualitative defects of Tregs in SLE patients with clinical data. Finally, this study will also allow one to experimentally abrogate potential defects of Treg in SLE patients. This might provide the basis for new therapeutic concepts in the treatment of SLE and other autoimmune diseases.