Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory signaling pathway in autoimmune arthritis.
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 is a promising therapeutic approach for rheumatoid arthritis.
Xue
Hong
H
Department of Immunology, Beijing 307 Hospital, Academy of Medical Sciences, Beijing, People's Republic of China.
Liang
Fei
F
Liu
Nan
N
Song
Xinqiang
X
Yuan
Fang
F
Luo
Yuan
Y
Zhao
Xiao
X
Long
Juan
J
Sun
Yuying
Y
Xi
Yongzhi
Y
D036002:ADP Ribose Transferases / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D018501:Antirheumatic Agents / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000517:prevention & control*; D051940:B7-2 Antigen / Q000008:administration & dosage* / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005098:Exotoxins / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000008:administration & dosage* / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D018501:Antirheumatic Agents; D051940:B7-2 Antigen; D001427:Bacterial Toxins; D018106:CD28 Antigens; D016207:Cytokines; D005098:Exotoxins; D019444:Vaccines, DNA; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A