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Departments of
*
Immunohematology and Blood Transfusion,
Human and Clinical Genetics, and
Pathology, Leiden University Medical Center, Leiden, The Netherlands; and
Institut National de la Santé et de la Recherche Médicale, Unité 520, Section Recherche, Institut Curie, Paris, France
Dendritic cells (DCs) require a maturation signal to acquire
efficient CTL-priming capacity. In vitro Fc
R-mediated
internalization of Ag-Ab immune complexes (ICs) can induce maturation
of DCs. In this study, we show that IC-induced DC maturation in vitro
enables DCs to prime peptide-specific CD8+ CTLs in vivo,
independently of CD4+ Th cells. Importantly,
OVA/anti-OVA IC-treated DCs not only primed CD8+ CTLs
to an exogenously loaded peptide nonrelated to OVA, but also
efficiently primed CTLs against the dominant CTL epitope derived from
the OVA Ag present in the ICs. Our studies show that ICs fulfill a dual
role in priming of CD8+ CTL responses to exogenous Ags:
enhancement of Ag uptake by DCs and activation of DCs, resulting in
"license to kill." These findings indicate that the presence of
specific Abs can crucially affect the induction of cytotoxic cellular
responses.
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