Constitutive versus activation-dependent cross-presentation of immune complexes by CD8(+) and CD8(-) dendritic cells in vivo.
Murine splenic dendritic cells (DCs) can be divided into two subsets based on CD8alpha 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 FcgammaRs, 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.
den Haan
Joke M M
JM
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7370, USA.
Bevan
Michael J
MJ
D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology
D000936:Antigen-Antibody Complex; D017452:Receptors, IgG; D010047:Ovalbumin