Delivery of liposome-encapsulated HIV type 1 proteins to human dendritic cells for stimulation of HIV type 1-specific memory cytotoxic T lymphocyte responses

An important aspect of vaccine development involves delivery of antigens to antigen-presenting cells for the induction of potent antigen-specific T ly mphocyte responses. We investigated the effect of a cationic liposome, lipo fectin, on delivery of whole proteins to human dendritic cells (DCs) derive d from blood mononuclear cells by culture in interleukin 4 and granulocyte- monocyte colony-stimulating factor for stimulation of human immunodeficienc y virus type 1 (HIV-1)-specific memory cytotoxic T lymphocyte (CTL) respons es, Delivery of HIV-1 Gag, Pol, and Env proteins to DCs by lipofectin stimu lated greater anti-HIV-1 memory CTL responses in cells from HIV-1-infected subjects than those induced by DCs loaded with protein alone. The CTLs were CD8(+) and HLA class I restricted, Antigen presentation was enhanced by ch loroquine, but blocked by brefeldin A and peptide aldehyde inhibitors of pr oteasomes, indicating that the classic MHC class I cytosolic pathway was us ed for processing and presentation of HIV-1. protein by the DCs, Stimulatio n of anti-HIV-1 CTLs by this safe, inexpensive, and broadly applicable appr oach may be used in DC-based therapies for HIV-1 infection.