Publication in Blood

Tel en Schriebelt

In the latest issue of Blood, Gerty Schreibelt and Jurjen Tel (both Dept. of Tumor Immunology) published their findings entitled "Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets".

The cross-presentation of exogenous antigens (Ags) on MHC class I is essential for the initiation of an effective adaptive immune response against tumors. Therefore cross-presentation has been extensively studied and the cell type and conditions best facilitating cross-presentation has become the holy grail of (tumor) immunology. Until now, most cross-presentation studies are based on murine DC subsets or on human ex vivo generated monocyte-derived DCs. The cross-presenting capacities of naturally occurring human DC subsets has gained interest over the past years but fast progression in the field has been restricted by the scarceness of especially pDCs and BDCA3+ mDCs.

Furthermore, the use of different Ags and Ag sources like proteins, cell lysates, peptides, and virus infected apoptotic cells, in combination with small comparative studies made the results hard to compare and to draw strong conclusions. In their paper, Tel and Schreibelt investigated, for the first time, not only the capacity of all four natural circulating DC subsets to cross-present exogenous Ags from various sources in combination with TLR agonists as adjuvants but also their ability to take up and process different Ags both in soluble as particulate form. They show that, although human pDCs take up significant less Ags than their myeloid counterparts, pDCs effectively cross-present and cross-prime soluble and cell-associated tumor Ags to CD8+ T cells.

These findings put human pDCs forward as potent activators of anti-tumor responses, that efficiently present exogenous Ags to T cells in combination with a high type I IFN production to further activate components of both the innate and adaptive immune system.

Jurjen Tel*, Gerty Schreibelt*, Simone P. Sittig, Till S. M. Mathan, Sonja I. Buschow, Luis J. Cruz, Annechien J.A. Lambeck, Carl G. Figdor*, I. Jolanda M. de Vries*. Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets. Blood 2013 Jan 17;121(3):459-67


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