Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets

J. Tel, G. Schreibelt, Simone P Sittig, Till S M Mathan, Sonja I Buschow, L.-J. Cruz, A.J.A. Lambeck, C.G. Figdor, I.J.M. de Vries

Research output: Contribution to journalArticleAcademicpeer-review

105 Citations (Scopus)

Abstract

In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16(+), CD1c(+), and BDCA-3(+) myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8(+) T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c(+) and BDCA3(+) mDCs, pDCs induce potent Ag-specific CD4(+) and CD8(+) T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4(+) and CD8(+) T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3(+) mDCs. These findings, and the fact that pDCs outnumber BDCA3(+) mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8(+) T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.

Original languageEnglish
Pages (from-to)459-67
Number of pages9
JournalBlood : the Journal of Hematology
Volume121
Issue number3
DOIs
Publication statusPublished - 17 Jan 2013
Externally publishedYes

Keywords

  • Adaptive Immunity
  • Antigen Presentation
  • Antigens, CD1
  • Antigens, Neoplasm
  • Antigens, Surface
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cells, Cultured
  • Dendritic Cells
  • GPI-Linked Proteins
  • Glycoproteins
  • Humans
  • Immunity, Innate
  • Immunotherapy
  • Interferon-gamma
  • Myeloid Cells
  • Neoplasms
  • Receptors, IgG
  • Solubility
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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