The Journal of Experimental Medicine
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Published 17 June 2002. doi:10.1084/jem.20020338
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© Rockefeller University Press, 0022-1007/2002/6/1653/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 12, June 17, 2002 1653-1659

Brief Definitive Report

Inducing Tumor Immunity through the Selective Engagement of Activating Fc{gamma} Receptors on Dendritic Cells

Alexis M. Kalergis and Jeffrey V. Ravetch

Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021

Address correspondence to either J.V. Ravetch or A.M. Kalergis, The Rockefeller University, 1230 York Ave., Box 98, New York, NY 10021. Phone: 212-327-7321; Fax: 212-327-7318; E-mail: ravetch{at}rockefeller.edu or kalergi{at}rockefeller.edu

Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by Fc{gamma}RIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory Fc{gamma}Rs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating Fc{gamma}Rs. This mechanism suggests a novel approach to the development of tumor vaccines.

Key Words: immune complexes • Fc{gamma} receptors • DC maturation • inhibitory/activating receptor pairs • T cell immunity


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