International Immunology, Vol. 12, No. 5, 691-700,
May 2000
© 2000 Japanese Society for Immunology
Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens
1 Laboratory of Molecular Immunoregulation,
2 Intramural Research Support Program, SAIC Frederick,
3 Laboratory of Leukocyte Biology, and
5 Department of Experimental Transplantation and Immunology, Medicine Branch, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
Correspondence to: J. J. Oppenheim
Defensins released by neutrophils are able to kill a broad spectrum of microbes. 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 spleen cell proliferation and IFN-
production. This led us to examine the effects of human defensins on specific immune responses in vivo. BALB/c mice were immunized with 50 µg of keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide and administered with defensins in aqueous solution. Intraperitoneal administration of defensins significantly increased the production of KLH-specific IgG1, IgG2a and IgG2b antibodies 14 days after immunization. In vitro splenic KLH-specific proliferative responses were higher in mice treated with KLH and defensins than in those treated with KLH alone. Increased IFN- and, to a lesser extent, IL-4 production were also detected in the supernatants of ex vivoKLH-activated spleen cells from mice treated with defensins. Finally, defensins significantly enhanced the antibody response to a syngeneic tumor antigen, lymphoma Ig idiotype and also augmented 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 production. Thus, defensins appear to function as neutrophil-derived signals that promote adaptive immune responses.
Keywords: antibody formation, cytokine, IFN-, IL-4, tumor antigen
4 Genetics Institute, 87 Cambridge Park Drive, Cambridge, MA 02140, USA
Transmitting author: M. Feldman
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