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. Short-term 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.


CONCLUSIONS
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.
Hahn
Bevra H
BH
Division of Rheumatology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1670, USA. bhahn@mednet.ucla.edu <bhahn@mednet.ucla.edu>
Anderson
Marissa
M
Le
Elizabeth
E
La Cava
Antonio
A
D000328:Adult; D000974:Antibodies, Antinuclear / Q000494:pharmacology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D050440:Immunoglobulin Subunits / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
D000974:Antibodies, Antinuclear; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050440:Immunoglobulin Subunits; D053645:Interleukin-2 Receptor alpha Subunit