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Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
Dendritic cells (DC) can be generated in vitro from monocytes
(M-DC) or from CD34+ hemopoietic progenitor cells (CD34-DC)
but their precursors are not equivalent cells, prompting a comparison
of the functional capacities of these APC. Both types of DCs
established from the same individuals using the same cytokines
displayed a comparable phenotype of mature DC (CD1a+,
CD83+, CD86+, CD4+,
HLA-DR++, CD14-, CD15- ) and were
equally potent stimulators of allogeneic T cell proliferation, being
both more powerful than immature M-DCs. An autologous panel of APCs
produced in HLA-A2+ individuals, including CD34-DC, M-DC,
monocytes, and EBV-lymphoid cell line was comparatively evaluated for
presentation of the Erb-B2 peptide E75 to a CTL line. After short
exposures (5 h) to E75-loaded APCs, similar levels of intracellular
IFN-
were induced in Ag-specific CD8+ T cells regardless
of APC type. In sustained cultures (4–14 days), more Ag-specific T
cells were obtained when peptide was presented on CD34-DC (p <
0.05) rather than on M-DC, EBV-lymphoid cell lines, or monocytes, and
these effects were dose-dependent. Activated T cells expressed 4-1BB,
and the presence of 4-1BB-Ig fusion protein partially blocked
Ag-specific CD8+ cell activation after CD34-DC or M-DC
presentation. Our results show that 34-DC have a preferential capacity
to activate CD8+ T cells and that this property is not
strictly correlated to their ability to induce allogeneic T cell
proliferation but due to mechanisms that remain to be
defined.
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