Induction of primary human CD8(+) T lymphocyte responses in vitro using dendritic cells

The ability of two different human professional APCs, specifically macropha ges (M phi) and dendritic cells (DC), to stimulate primary responses in hum an CD8(+) T lymphocytes was examined using both allogeneic and Ag-pulsed au tologous APCs, CTL responses in CD8(+) T lymphocytes isolated from HIV-unin fected donors were evaluated against six different HIV epitopes that are re stricted by four different HLA alleles using autologous human PBMC-derived M phi and DCs for primary stimulation. In a side-by-side experiment, immatu re DCs. but not M phi, were able to prime a CTL response against the B14-re stricted p24(gag) 298-306 epitope; mature DCs were also able to prime a res ponse against this epitope, In addition, DCs were capable of priming CD8(+) CTL responses against the BS-restricted p24(gag) 259-267 epitope, In contr ast, M phi were unable to prime strong CTL responses against other epitopes , Since the Ag-specific cytotoxic responses required subsequent rounds of r estimulation before they could be detected, the ability of the allogeneic M phi and DCs to directly prime CD8(+) T lymphocyte responses without subseq uent restimulation was examined. Similar to the aforementioned peptide-spec ific results, DCs were more efficient than M phi in priming both allogeneic proliferative and cytotoxic responses in human CD8(+) T lymphocytes. Colle ctively, these results promote an enhanced status for DCs in the primary st imulation of human CD8(+) T lymphocytes.