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CD69 targeting differentially affects the course of collagen‐induced arthritis
Author(s) -
Sancho David,
Gómez Manuel,
Martinez del Hoyo Gloria,
Lamana Amalia,
Esplugues Enric,
Lauzurica Pilar,
MartinezA Carlos,
SánchezMadrid Francisco
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1205749
Subject(s) - cd69 , arthritis , adoptive cell transfer , immunology , immune system , biology , monoclonal antibody , inflammation , proinflammatory cytokine , tumor necrosis factor alpha , t cell , il 2 receptor , antibody
CD69 expression is induced following activation of leukocytes at inflammatory sites and plays a negative regulatory role in the development of collagen‐induced arthritis (CIA). To evaluate potential strategies of CD69 targeting in chronic inflammatory diseases, two different anti‐CD69 mAbs were generated and their effects on CIA were studied. Administration of the IgG1 anti‐CD69 mAb 2.2 to DBA/1 mice with CIA led to an exacerbation of the disease, correlated with down‐modulation of CD69 from the cell surface, and reproduced the phenotype of the CD69(−/−) mouse in wild‐type animals. In contrast, treatment with the IgG2a anti‐CD69 mAb 2.3 was effective in ameliorating CIA when administered in the early or intermediate phases of the disease, causing a decreased production of proinflammatory cytokines in inflammatory foci. Monoclonal antibody 2.3 induces partial depletion of CD69+ cells in vivo. Moreover, adoptive transfer of type‐II collagen (CII)‐sensitized cells treated with mAb 2.3 to deplete CD69+ cells did not result in arthritis. The attenuation of inflammation correlates with reduced lymphocyte proliferative response in response to CII and with a reduction in the frequency of CII‐specific T cells producing IFN‐γ. We thus conclude that CD69 targeting by mAbs can either enhance or dampen the immune response.