CYTOKINE EXPRESSION BY HUMAN PERIPHERAL-BLOOD DENDRITIC CELLS STIMULATED IN-VITRO WITH HIV-1 AND HERPES-SIMPLEX VIRUS

Dendritic cells are potent stimulators of Ag-specific T cell responses and have been implicated in the pathogenesis of HIV-1 and other viral infections. Although cytokines may be involved in bath of these proce sses, there is little information on the expression of cytokines by hu man blood dendritic cells. We characterized cytokine gene and protein expression in dendritic cells that were purified from normal human PBM C by flow cytometry and stimulated in vitro for up to 24 h with HIV-1 or herpes simplex virus (HSV). The unstimulated, uncultured dendritic cells were defined by their phenotype (HLA DR(+) CD3(-.)CD19(-) CD16(- )CD56(-) CD14(-)) and distinct morphology, lack of mRNA expression for CD3, CD14 and CD19, and presence of mRNA for CD4 and CD83. The purifi ed dendritic cells also expressed CD4 (70-90%), CD33 (36-48%), and CD1 1c (44-54%); lacked CD1a expression (<1 %); and were potent stimulator s of an allogeneic MLR. The stimulated dendritic cells expressed mRNA for IFN-cu, IL-1 alpha, IL-1 beta, IL-6, IL-10, IL-12, GM-CSF, and TNF -alpha within 4 to 12 h as determined by reverse transcription-PCR, wi th higher Bevels induced tay HSV compared with HlV-1 strains IIIb or B aL. In contrast, the dendritic cells produced detectable protein only for IFN-alpha and IL-6 in response to HIV-1 or HSV, and IL-1 beta in r esponse to HSV within 24 h. There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either m ock stimulated or stimulated with HIV-1 or HSV for 24 h. Production of IFN-alpha, IL-1 beta, and IL-6 beta, dendritic cells may be important to the immunologic function of these cells and their role in the path ogenesis of HIV-1 and HSV infections.