DNA Vaccination with Heat Shock Protein 70 Protects (NZB x NZW)F 1 Mice from Systemic Lupus Erythematosus

OBJECTIVE: To address whether a targeted modulation of the abnormal expression of heat shock protein (HSP)70 and autoantibodies against this molecule in systemic lupus erythematosus (SLE) can influence disease. METHODS: Lupus-prone (NZB x NZW)F1 mice that had been DNA-vaccinated with plasmids encoding HSP70 or controls were monitored for lupus disease parameters including anti-dsDNA autoantibodies and cytokines by enzyme-linked immunosorbent assay (ELISA), and for kidney function and pathology. Evaluation of the phenotypic and numeric changes of relevant immune cells by flow cytometry was paralleled by assessments of cell function. RESULTS: Mice that had been DNA-vaccinated with HSP70 but not controls displayed a marker suppression of anti-dsDNA antibody production, had a reduced renal disease, and anti-inflammatory responses associated with a significantly extended survival. These protective effects in HSP70-vaccinated mice associated with an induction of tolerogenic immune responses and an expansion of functional T regulatory cells. CONCLUSION: DNA vaccination with HSP70 suppresses murine lupus by inducing tolerogenic immune responses and anti-inflammatory immune responses that associate with reduced disease manifestations and increased mice survival.