The Journal of Experimental Medicine
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Published online 9 September 2002 doi:10.1084/jem.20020295
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© Rockefeller University Press, 0022-1007/2002/9/817/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 6, September 16, 2002 817-827
Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8- Dendritic Cells In Vivo

Joke M.M. den Haan and Michael J. Bevan

Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

Address correspondence to M.J. Bevan, Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195-7370. Phone: 206-685-3610; Fax: 206-685-3612; E-mail: mbevan{at}u.washington.edu

Murine splenic dendritic cells (DCs) can be divided into two subsets based on CD8{alpha} expression, but the specific role of each subset in stimulation of T cells is largely unknown. An important function of DCs is the ability to take up exogenous antigens and cross-present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells. We previously demonstrated that, when cell-associated ovalbumin (OVA) is injected into mice, only the CD8+ DC subset cross-presents OVA in the context of MHC class I. In contrast to this selectivity with cell-associated antigen, we show here that both DC subsets isolated from mice injected with OVA/anti-OVA immune complexes (OVA-IC) cross-present OVA to CD8+ T cells. The use of immunoglobulin G Fc receptor (Fc{gamma}R) common {gamma}-chain–deficient mice revealed that the cross-presentation by CD8- DCs depended on the expression of {gamma}-chain–containing activating Fc{gamma}Rs, whereas cross-presentation by CD8+ DCs was not reduced in {gamma}-chain–deficient mice. These results suggest that although CD8+ DCs constitutively cross-present exogenous antigens in the context of MHC class I molecules, CD8- DCs only do so after activation, such as via ligation of Fc{gamma}Rs. Cross-presentation of immune complexes may play an important role in autoimmune diseases and the therapeutic effect of antitumor antibodies.

Key Words: antigen presentation • cytotoxic T lymphocyte • cross-priming • dendritic cell • Fc receptors


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