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Hum Gene Ther. 2011 Jan;22(1):65-76. doi: 10.1089/hum.2010.110. Epub 2010 Dec 6.

Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory signaling pathway in autoimmune arthritis.

Author information

1
Department of Immunology, Beijing 307 Hospital, Academy of Medical Sciences, Beijing, People's Republic of China.

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.

PMID:
20695769
DOI:
10.1089/hum.2010.110
[Indexed for MEDLINE]

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