Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells

Abstract

Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating antigens is difficult to achieve. Exogenous antigens, such as viral proteins and peptides, normally induce CD4+ T-cell responses unless appropriately delivered to the major histocompatibility complex class I antigen presentation pathway. In vitro studies performed to address this issue revealed a similar scenario, and primary CTL induction with nonreplicating antigens has rarely been reported. This study demonstrated primary antiviral CTL induction in vitro with exogenous antigens delivered in vivo to dendritic cells. This study also evaluated the efficacy of glycoprotein B peptide (free or encapsulated in liposomes), peptide-tripalmitoyl-S-glyceryl cysteinyl conjugate (acylpeptide), and glycoprotein B protein encapsulated in pH-sensitive liposomes as antigen delivery vehicles. Our results show that higher levels of cytotoxicity against herpes simplex virus type 1 resulted from exposure of dendritic cells to peptide-tripalmitoyl-S-glyceryl cysteinyl in liposomes. Macrophages treated in a similar manner were not effective stimulators for primary CTL induction. Our data have relevance to the understanding of mechanisms of antigen processing and presentation and the design of antiviral vaccines.