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 lymphocyte responses. We investigated the effect of a cationic liposome, lipofectin, on delivery of whole proteins to human dendritic cells (DCs) derived from blood mononuclear cells by culture in interleukin 4 and granulocyte-monocyte colony-stimulating factor for stimulation of human immunodeficiency virus type 1 (HIV-1)-specific memory cytotoxic T lymphocyte (CTL) responses. Delivery of HIV-1 Gag, Pol, and Env proteins to DCs by lipofectin stimulated 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 chloroquine, but blocked by brefeldin A and peptide aldehyde inhibitors of proteasomes, indicating that the classic MHC class I cytosolic pathway was used for processing and presentation of HIV-1 protein by the DCs. Stimulation of anti-HIV-1 CTLs by this safe, inexpensive, and broadly applicable approach may be used in DC-based therapies for HIV-1 infection.
Zheng
L
L
Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Huang
X L
XL
Fan
Z
Z
Borowski
L
L
Wilson
C C
CC
Rinaldo
C R
CR
D000328:Adult; D017951:Antigen Presentation / Q000187:drug effects; D000998:Antiviral Agents / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D015331:Cohort Studies; D003713:Dendritic Cells / Q000187:drug effects / Q000821:virology*; D015497:HIV-1; D018451:Homosexuality, Male; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008081:Liposomes; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000008:administration & dosage* / Q000276:immunology
D000998:Antiviral Agents; D008081:Liposomes; D014764:Viral Proteins; D020126:Brefeldin A; D002738:Chloroquine