Publication
Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis
dc.contributor.author | Raposo, BR | |
dc.contributor.author | Rodrigues-Santos, P | |
dc.contributor.author | Carvalheiro, H | |
dc.contributor.author | Água-Doce, AM | |
dc.contributor.author | Carvalho, L | |
dc.contributor.author | Pereira da Silva, JA | |
dc.contributor.author | Graça, L | |
dc.contributor.author | Souto-Carneiro, MM | |
dc.date.accessioned | 2011-11-07T14:56:09Z | |
dc.date.available | 2011-11-07T14:56:09Z | |
dc.date.issued | 2010 | |
dc.description.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 mAb-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. | por |
dc.identifier.citation | Arthritis Rheum. 2010 Oct;62(10):2953-62. | por |
dc.identifier.uri | http://hdl.handle.net/10400.4/1111 | |
dc.language.iso | eng | por |
dc.peerreviewed | yes | por |
dc.publisher | Wiley | por |
dc.subject | Artrite Experimental | por |
dc.subject | Antigénio CD8 | por |
dc.subject | Anticorpos Monoclonais | por |
dc.title | Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis | por |
dc.type | journal article | |
dspace.entity.type | Publication | |
rcaap.rights | openAccess | por |
rcaap.type | article | por |