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Updated: Aug 9, 2026

An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets
Published on: April 18, 2016
Constitutive versus activation-dependent cross-presentation of immune complexes by CD8(+) and CD8(-) dendritic cells
Joke M M den Haan1, Michael J Bevan
1Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7370, USA.
Insights
Murine splenic dendritic cells (DCs) have distinct roles in T cell stimulation. CD8(+) DCs constitutively cross-present antigens, while CD8(-) DCs require activation via Fc receptors for antigen cross-presentation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial for T cell activation.
- Murine splenic DCs comprise CD8alpha(+) and CD8alpha(-) subsets with distinct functions.
- Cross-presentation of exogenous antigens via MHC class I to CD8(+) T cells is a key DC function.
Purpose of the Study:
- To investigate the differential roles of CD8alpha(+) and CD8alpha(-) DCs in antigen cross-presentation.
- To determine the mechanisms by which different DC subsets present cell-associated antigens versus immune complexes.
Main Methods:
- Utilized ovalbumin (OVA) and OVA/anti-OVA immune complexes (OVA-IC) for antigen administration in mice.
- Employed CD8alpha expression to distinguish DC subsets.
- Used immunoglobulin G Fc receptor (Fc(gamma)R) common gamma-chain-deficient mice to assess FcgammaR involvement.
Main Results:
- CD8alpha(+) DCs selectively cross-presented cell-associated OVA.
- Both CD8alpha(+) and CD8alpha(-) DCs cross-presented OVA from OVA-IC.
- Cross-presentation by CD8alpha(-) DCs required FcgammaRs, unlike CD8alpha(+) DCs.
Conclusions:
- CD8alpha(+) DCs constitutively cross-present exogenous antigens.
- CD8alpha(-) DCs require activation, such as FcgammaR ligation, for cross-presentation.
- Immune complex cross-presentation by DCs may impact autoimmune diseases and cancer immunotherapy.
Abstract:
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.
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