Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8− Dendritic Cells In Vivo
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.
- Amsterdam UMC, location VUmc Netherlands
- University of Mary United States
- Howard Hughes Medical Institute United States
- University of Washington United States
Antigen Presentation, Ovalbumin, Receptors, IgG, Antigen-Antibody Complex, Dendritic Cells, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Article, Mice, Inbred C57BL, Mice, Animals
Antigen Presentation, Ovalbumin, Receptors, IgG, Antigen-Antibody Complex, Dendritic Cells, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Article, Mice, Inbred C57BL, Mice, Animals
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