Anti-DNA Ig peptides promote Treg cell activity in systemic lupus erythematosus patients

Objective. Treg cells oppose autoreactive responses in several autoimmune diseases, and their frequency is reduced in systemic lupus erythematosus (SLE). In murine lupus models, treatment with anti-DNA Ig-based peptides can expand the number of Treg cells in vivo. This study was undertaken to test the possibility that functional human Treg cells can be induced by exposure to anti-DNA Ig-based peptides. Methods. Peripheral blood mononuclear cells were isolated from 36 lupus patients and 32 healthy individuals matched for ethnicity, sex, and age. Shortterm culture experiments in the presence of several independent stimuli including anti-DNA Ig peptides were followed by flow cytometric analysis for identification of CD4+,CD25(high) T cells, cell sorting for in vitro suppression assays, and analysis of correlations between the expression of forkhead box P3 (FoxP3) and serologic and clinical characteristics of the SLE patients. Results. The number of in vitro CD4+,CD25(high) T cells increased after culture with anti-DNA Ig peptides in the SLE patients, but not in the controls. The expanded CD4+,CD25(high) T cells required FoxP3 for cell contact-mediated suppression of proliferation and interferon-gamma production in target CD4+,CD25- T cells. The induction of FoxP3 in SLE Treg cells occurred only in seropositive Patients, and was correlated with anti-DNA and IgG serum titers. Conclusion. These results suggest a new modality to reverse the functional deficit of Treg cells in SLE patients with positive autoimmune serology, and identify a new strategy to enhance immunoregulatory T cell activity in human SLE.