title: 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 is a promising therapeutic approach for rheumatoid arthritis.
authors.affiliation: Department of Immunology, Beijing 307 Hospital, Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Fei
authors.initials: F
authors.lastname: Liang
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Song
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Long
authors.forename: Yuying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Xi
mesh_terms: 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
chemical_list: 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