Human Cytomegalovirus pp65- and Immediate Early 1 Antigen-Specific HLA Class I-Restricted Cytotoxic T Cell Responses Induced by Cross-Presentation of Viral Antigens

摘要: Dendritic cells (DCs) play a pivotal role in the development of anti-viral CD8(+) CTL responses. This is straightforward if they are directly infected with virus, but less clear response to viruses that cannot productively infect DCS: Human CMV (HCMV) shows strain-specific cell tropism: fibroblast (Fb)-adapted laboratory strains (AD169) and recent clinical isolates do not DCs, whereas endothelial cell-adapted (TB40/E) result productive lytic DC infection. However, we show here uninfected DCs induce T cytotoxicity IFN-gamma production against HCMV pp65 immediate early 1 Ags following vitro coculture HCMV-AD169-infected Fbs, regardless HLA type these FBS: stimulation was inhibited by pretreatment cytochalasin B or brefeldin A, indicating phagosome/endosome cytosol pathway. HCMV-infected Fbs were apoptotic as measured annexin V binding, induction apoptosis did augment suggesting mechanism other than initiation cross-presentation. Furthermore, provided maturation signal for immature during coculture, evidenced increased CD83 class II expression. Cross-presentation host enables professional APCs bypass some evasion mechanisms has developed avoid recognition. It may also serve explain presence Ag-specific CTLs face pp65-induced inhibition Ag presentation at level cell.