ADMINISTRATION OF ANTIBODIES TO HYALURONANRECEPTOR (CD44) DELAYS THE START AND AMELIORATES THE SEVERITY OF COLLAGEN-II ARTHRITIS

Hyaluronanreceptor (CD44) has been shown to be involved in lymphocyte homing during normal leucocyte circulation and during leucocyte extrav asation into sites of tissue inflammation. In addition, interaction wi th CD44 molecule induces T-cell activation and production of cytokines , such as interferon-gamma. In this study we have examined what influe nce interaction with the CD44 receptor would have on collagen II-induc ed arthritis in mice. Mice were immunized with rat collagen II and adm inistered with injections of a monoclonal anti-CD44 antibody. Seventee n days after the outbreak of the disease, all of the anti-CD44 treated animals remained clinically healthy, whereas 37% of the controls disp layed arthritis (P < 0.001). Ten days later the prevalence of arthriti s was 26% and 65% (P < 0.05), respectively. Furthermore, the severity of the arthritis was significantly ameliorated by the anti-CD44 treatm ent. Serum levels of interferon-gamma were significantly higher in col lagen II immunized animals having been treated with anti-CD44, compare d to the controls. Delayed-type hypersensitivity (DTH) response was si gnificantly decreased in the anti-CD44 treated animals, indicating a f unctional suppression of T cells. In contrast, T cell independent expe rimental inflammation was not affected by the administration of CD44 a ntibodies. Our results suggest that interaction with CD44 down-regulat es T lymphocyte/monocyte mediated inflammatory reaction, possibly by t riggering of interferon-gamma release.