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*
Laboratory of Cellular Physiology and Immunology and
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10021;
Molecular Immunology Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and
§
Department of Virology, National Public Health Institute, Helsinki Finland
It is critical to identify the developmental stage of dendritic
cells (DCs) that is most efficient at inducing CD8+ T cell
responses. Immature DCs can be generated from monocytes with GM-CSF and
IL-4, while maturation is accomplished by the addition of stimuli such
as monocyte-conditioned medium, CD40 ligand, and LPS. We evaluated the
ability of human monocytes and immature and mature DCs to induce
CD8+ effector responses to influenza virus Ags from resting
memory cells. We studied replicating virus, nonreplicating virus, and
the HLA-A*0201-restricted influenza matrix protein peptide. Sensitive
and quantitative assays were used to measure influenza A-specific
immune responses, including MHC class I tetramer binding assays,
enzyme-linked immunospot assays for IFN-
production, and generation
of cytotoxic T cells. Mature DCs were demonstrated to be superior to
immature DC in eliciting IFN- production from CD8+
effector cells. Furthermore, only mature DCs, not immature DCs, could
expand and differentiate CTL precursors into cytotoxic effector cells
over 7 days. An exception to this was immature DCs infected with live
influenza virus, because of the virus’s known maturation effect.
Finally, mature DCs pulsed with matrix peptide induced CTLs from highly
purified CD8+ T cells without requiring CD4+ T
cell help. These differences between DC stages were independent of Ag
concentrations or the number of immature DCs. In contrast to DCs,
monocytes were markedly inferior or completely ineffective stimulators
of T cell immunity. Our data with several qualitatively different
assays of the memory CD8+ T cell response suggest that
mature cells should be considered as immunotherapeutic adjuvants for Ag
delivery.
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