Pivotal Advance: CD69 targeting differentially affects the course of collagen-induced arthritis

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 CIIspecific T cells producing IFN. We thus conclude that CD69 targeting by mAbs can either enhance or dampen the immune response. J. Leukoc. Biol. 80: 1233–1241; 2006.