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Divisions of
*
Immunology, Allergy and Infectious Diseases (DIAID), and
General Dermatology, Department of Dermatology, University of Vienna Medical School, Vienna, Austria
Two types of dendritic cells (DC) are circulating in human blood
and can be identified by their differential expression of the myeloid
Ag CD11c. In this study, we show that CD11c- peripheral
blood (PB)-DC correspond to plasmacytoid DC of lymphoid tissue not only
by their surface Ag expression profile but, more impressively, by their
peculiar ultramorphology. We also demonstrate that CD11c-
and CD11c+ DC differ in the quality of their response to
and in their requirement for certain cytokines. Freshly isolated
CD11c- cells depend on IL-3 for survival and use autocrine
or exogenous TNF-
as maturation signal, leading to the appearance of
a highly dendritic phenotype, the up-regulation and redistribution of
MHC class II from lysosomal compartments to the plasma membrane, the
increased expression of costimulatory molecules, and the switch from a
high Ag-processing to a low Ag-processing/potent accessory cell mode.
Surprisingly, IL-4 efficiently killed freshly isolated
CD11c- PB-DC, but did not impair the viability
of CD11c+ PB-DC and, together with GM-CSF, induced
maturation of these cells. A direct functional comparison revealed that
neo-Ag-modified and subsequently matured
CD11c- but to a lesser extent
CD11c+ DC were able to prime naive Ag-specific
CD4+ T cells. Our findings show that two diverse DC
types respond to certain T cell-derived cytokines in a differential
manner and, thus, suggest that suppression or activation of
functionally diverse DC types may be a novel mechanism for the
regulation of the quantity and quality of immune
responses.
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