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*
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212; and
Division of Immunology and Rheumatology, Department of Internal Medicine, University of Missouri School of Medicine, and the Medical Research Service, Veterans Affairs Medical Center, Columbia, MO 65212
The ability of two different human professional APCs, specifically
macrophages (M
) and dendritic cells (DC), to stimulate primary
responses in human CD8+ T lymphocytes was examined using
both allogeneic and Ag-pulsed autologous APCs. CTL responses in
CD8+ T lymphocytes isolated from HIV-uninfected donors were
evaluated against six different HIV epitopes that are restricted by
four different HLA alleles using autologous human PBMC-derived M and
DCs for primary stimulation. In a side-by-side experiment, immature
DCs, but not M, were able to prime a CTL response against the
B14-restricted p24gag 298–306 epitope; mature DCs were also
able to prime a response against this epitope. In addition, DCs were
capable of priming CD8+ CTL responses against the
B8-restricted p24gag 259–267 epitope. In
contrast, M were unable to prime strong CTL responses against other
epitopes. Since the Ag-specific cytotoxic responses required subsequent
rounds of restimulation before they could be detected, the ability of
the allogeneic M and DCs to directly prime CD8+ T
lymphocyte responses without subsequent restimulation was examined.
Similar to the aforementioned peptide-specific results, DCs were more
efficient than M in priming both allogeneic proliferative and
cytotoxic responses in human CD8+ T lymphocytes.
Collectively, these results promote an enhanced status for DCs in the
primary stimulation of human CD8+ T
lymphocytes.
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