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Title: Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis
Author: Raposo, Bruno R.
Rodrigues-Santos, Paulo
Carvalheiro, Helena
Água-Doce, Ana M.
Carvalho, Lina
Pereira da Silva, José A.
Graça, Luís
Souto-Carneiro, M. Margarida
Keywords: Antigens, CD8
Antibodies, monoclonal
Issue Date: Oct-2010
Publisher: Wiley-Blackwell for American College of Rheumatology
Citation: Arthritis and Rheumatism - Vol. 62, No. 10, October 2010, pp 2953–2962
Abstract: Objective. CD8+ T cells are part of the T cell pool infiltrating the synovium in rheumatoid arthritis (RA). However, their role in the pathogenesis of RA has not been fully delineated. Using the K/BxN mouse model of spontaneous chronic arthritis, which shares many similarities with RA, we studied the potential of CD8 T cell depletion with monoclonal antibodies (mAb) to stop and reverse the progression of experimental arthritis. Methods. CD8+ T cells from the blood and articular infiltrate of K/BxN mice were characterized for cell surface phenotypic markers and for cytokine production. Additionally, mice were treated with specific anti-CD8 mAb (YTS105 and YTS169.4), with and without thymectomy. Results. CD8+ T cells from the peripheral blood and joints of K/BxN mice were mainly CD69+ and CD62L-CD27+ T cells expressing proinflammatory cytokines (interferon-γ [IFNγ], tumor necrosis factor α [TNFα], interleukin-17a [IL-17A], and IL-4), and granzyme B. In mice receiving anti-CD8 mAb, the arthritis score improved 5 days after treatment. Recovery of the CD8+ T cells was associated with a new increase in the arthritis score after 20 days. In thymectomized and anti-CD8 Ab–treated mice, the arthritis score improved permanently. Histologic analysis showed an absence of inflammatory infiltrate in the anti-CD8 mAb–treated mice. In anti-CD8 mAb–treated mice, the serologic levels of TNFα, IFNγ, IL-6, and IL-5 normalized. The levels of the disease-related anti–glucose-6-phosphate isomerase antibodies did not change. Conclusion. These results indicate that synovial activated effector CD8 T cells locally synthesize proinflammatory cytokines (IFNγ, TNFα, IL-17, IL-6) and granzyme B in the arthritic joint, thus playing a pivotal role in maintaining chronic synovitis in the K/BxN mouse model of arthritis.
Description: © 2010, American College of Rheumatology
Peer review: yes
DOI 10.1002/art.27729
ISSN: 0004-3591
Appears in Collections:IMM - Artigos em Revistas Internacionais

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