Potent Antirheumatic Activity of a New DNA Vaccine Targeted to B7-2/CD28 Costimulatory Signaling Pathway in Autoimmune Arthritis

Abstract Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4+CD25+ regulatory T (Tr) and CD8+CD28− suppressor T (Ts) cells to control autoreactive CD4+CD28+ Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4+/CD8+ cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current “gold standard” treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine...