Induction of cytotoxic T lymphocytes in vivo with protein antigen entrapped in membranous vehicles

Abstract

Intravenous administration of APC such as splenocytes loaded with a soluble protein Ag has been shown to prime for an Ag-specific CTL response. It is thought that the APC directly presents loaded Ag in a MHC-restricted manner. However, it is demonstrated in this study that allogeneic splenocytes, MHC-free RBC, and even synthetic lipid vesicles (liposomes) after loading with OVA can elicit an OVA-specific and MHC-restricted CTL response. Biodistribution studies of these Ag-associated vehicles showed that the liver, spleen, and lung were the major organs responsible to scavenge these carriers, suggesting that the monocyte-macrophage system was involved in the Ag presentation for CTL. Depletion of macrophages by a specific macrophage killer, Cl2MDP, containing liposomes, abolished the CTL induction by immunization with OVA Ag carried by these vehicles except the induction by syngeneic splenocytes. Thus, the syngeneic splenocytes present Ag directly to the T cells, but other membranous vehicles carry the Ag to the host APC including macrophages, which then present it to the T cells. These results indicate that formulation of an Ag in membranous/colloidal vehicles may be a way to prime for a CTL response.