Defensins act as potent adjuvants that promote cellular and humoral immuneresponses in mice to a lymphoma idiotype and carrier antigens

Defensins released by neutrophils are able to kill a broad spectrum of micr obes. They also induce leukocyte migration in vitro and elicit inflammatory leukocyte responses at s.c, injection sites in mice, In vitro experiments showed that human defensins enhanced concanavalin A-stimulated murine splee n cell proliferation and IFN-gamma production, This led us to examine the e ffects of human defensins on specific immune responses in vivo. BALB/c mice were immunized with 50 mu g of keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide and administered with defensins in aqueous solution. In traperitoneal administration of defensins significantly increased the produ ction of KLH-specific IgG1, IgG2a and IgG2b antibodies 14 days after immuni zation. In vitro splenic KLH-specific proliferative responses were higher i n mice treated with KLH and defensins than in those treated with KLH alone, Increased IFN-gamma and, to a lesser extent, IL-4 production were also det ected in the supernatants of ex vivo KLH-activated spleen cells from mice t reated with defensins, Finally, defensins significantly enhanced the antibo dy response to a syngeneic tumor antigen, lymphoma Ig idiotype and also aug mented resistance to tumor challenge. These results indicate that defensins act as potent immune adjuvants by inducing the production of lymphokines, which promote T cell-dependent cellular immunity and antigen-specific Ig pr oduction. Thus, defensins appear to function as neutrophil-derived signals that promote adaptive immune responses.