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 CD8α 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 (FcγR) common γ-chain–deficient mice revealed that the cross-presentation by CD8⁻ DCs depended on the expression of γ-chain–containing activating FcγRs, whereas cross-presentation by CD8⁺ DCs was not reduced in γ-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 FcγRs. Cross-presentation of immune complexes may play an important role in autoimmune diseases and the therapeutic effect of antitumor antibodies.