THE ROLE OF MACROPHAGES IN THE INDUCTION AND REGULATION OF IMMUNITY ELICITED BY EXOGENOUS ANTIGENS

Different delivery vehicles may target to different antigen presenting cells (APC) because of their composition, size and/or physical proper ties. In this study, we examined the priming of cytotoxic T lymphocyte (CTL) responses to a soluble exogenous protein in vivo, using various delivery vehicles. In addition, we determined the role of macrophages as APC in vivo for each of these delivery vehicles by comparing the i nduction of antigen-specific CTL and serum antibodies in normal and ma crophage-depleted mice. Influenza A virus-derived virosomes, liposomes and monophosphoryl lipid A/squalene (MPL/SQ) efficiently induced anti gen-specific CTL as well as antibody responses, of which virosomes pro ved to be the most efficient inducers. In mice that were immunized wit h cell-associated antigen, strong CTL responses but no antigen-specifi c antibodies were detectable, while aluminium hydroxide and aluminium phosphate elicited antigen-specific antibodies but no CTL responses; E limination of macrophages in vivo before immunization abrogated CTL re sponses induced with liposomes and MPL/SQ, but did not affect inductio n of antigen-specific CTL with virosomes or cell-associated antigen. I mportantly, serum antibody levels were not altered after macrophage de pletion, regardless of the delivery vehicle used, suggesting that in t he absence of macrophages, other APC may phagocytose the exogenous ant igens for major histocompatibility complex (MHC) class II processing a nd presentation. These results suggest that soluble exogenous antigens delivered in different carrier systems may be processed differently b y different APC in vivo for MHC class I-or class Ii-restricted present ation.