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 CII-specific T cells producing IFN-gamma. We thus conclude that CD69 targeting by mAbs can either enhance or dampen the immune response.
Sancho
David
D
Hospital Universitario de La Princesa,C/ Diego de León, 62, Madrid E-28006, Spain.
Gómez
Manuel
M
Martinez Del Hoyo
Gloria
G
Lamana
Amalia
A
Esplugues
Enric
E
Lauzurica
Pilar
P
Martinez-A
Carlos
C
Sánchez-Madrid
Francisco
F
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000633:toxicity; D007074:Immunoglobulin G / Q000276:immunology* / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D037181:Lectins, C-Type; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D024043:Collagen Type II; D007074:Immunoglobulin G; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens