Sancho, DavidGómez, ManuelMartinez del Hoyo, GloriaLamana Domínguez, AmaliaEsplugues, EnricLauzurica, PilarMartinez-A, CarlosSánchez-Madrid, Francisco2024-01-192024-01-192006David Sancho, Manuel Gómez, Gloria Martinez del Hoyo, Amalia Lamana, Enric Esplugues, Pilar Lauzurica, Carlos Martinez-A, Francisco Sánchez-Madrid, CD69 targeting differentially affects the course of collagen-induced arthritis, Journal of Leukocyte Biology, Volume 80, Issue 6, Dec 2006, Pages 1233–1241, https://doi.org/10.1189/jlb.12057490741-540010.1189/jlb.1205749https://hdl.handle.net/20.500.14352/94034CD69 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.engjournal article1938-3673https://doi.org/10.1189/jlb.1205749restricted access576.3577.27AntibodiesAutoimmunity,T cellsCytokinesChemokinesBiología celular (Biología)Inmunología2407 Biología Celular3109.03 Inmunología