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The Journal of Immunology, 2002, 168: 2240-2246.
Copyright © 2002 by The American Association of Immunologists

Antigen-Antibody Immune Complexes Empower Dendritic Cells to Efficiently Prime Specific CD8+ CTL Responses In Vivo1

Danita H. Schuurhuis2,*, Andreea Ioan-Facsinay2,{dagger}, Bas Nagelkerken{ddagger}, Jolien J. van Schip*, Christine Sedlik§, Cornelis J. M. Melief*, J. Sjef Verbeek{dagger} and Ferry Ossendorp3,*

Departments of * Immunohematology and Blood Transfusion, {dagger} Human and Clinical Genetics, and {ddagger} 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{gamma}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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