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More MS news articles for October 2002

Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8(+) and CD8(-) Dendritic Cells In Vivo

J Exp Med 2002 Sep 16;196(6):817-27
Den Haan JM, Bevan MJ.
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195.

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 (FcgammaR) 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 FcgammaRs.

Cross-presentation of immune complexes may play an important role in autoimmune diseases and the therapeutic effect of antitumor antibodies.