CORRELATION BETWEEN IN-VITRO AND IN-VIVO BEHAVIOR OF LIPOSOMAL ANTIGENS

Using conalbumin as a model antigen, we demonstrate in this paper that liposomal antigen differently influences the activation of the immune system depending on the mode of association of the antigen with the l iposomal vehicle whether it is by encapsulation or surface linkage. Th is conclusion is based on in vivo data showing that encapsulated antig en induces a short-lasting response dominated by IgG1 production while surface-linked antigen has a longer-lasting effect characterized by i ncreased production of IgM, IgG2a, IgG3 as well as of IgG1. The in viv o data were complemented by in vitro proliferation studies carried out on spleen cells or macrophage-depleted spleen cells obtained from mic e sensitized in vivo and rechallenged in vitro on day 4 following sens itization. Rechallenge was carried out in the absence or presence of a nti-IL-1. The data indicate that, in contrast to what is generally obs erved in vivo, liposomes alone potentiate spleen cell proliferative re sponse in a dose-dependent manner. This liposomal effect totally obscu res the antigen-specific proliferation that was expected with encapsul ated antigen without masking that induced by surface-linked antigen. T he mode of antigen association also influences anti-cytokine responsiv eness as demonstrated by the insensitivity of the surface-linked antig en response to the presence of anti-IL-1 and the significantly decreas ed response observed with encapsulated antigen under identical conditi ons. The response to both liposomal antigenic formulations was almost totally abolished in adherent cell-depleted cultures. The overall resu lts therefore suggest that encapsulated and surface-linked antigens ac tivated different immune pathways.