CD11c+ blood dendritic cells induce antigen-specific cytotoxic T lymphocytes with similar efficiency compared to monocyte-derived dendritic cells despite higher levels of MHC class I expression

J Immunother. 2006 Nov-Dec;29(6):596-605. doi: 10.1097/01.cji.0000211310.90621.5d.

Abstract

Dendritic cell (DC) immunotherapy for cancer has shown promising results in phase I and II clinical trials. Most studies have used monocyte-derived DCs (MoDCs) but their poor migratory capacity in vivo has emerged as a key issue. The natural circulating peripheral blood CD11c+ DC precursors (BDCs) may be an attractive alternative to MoDCs, as they can be isolated rapidly in sufficient quantities, and have superior migratory and T helper-1-inducing capacity in vitro. We performed the first comparative analysis of the ability of autologous BDCs and MoDCs in healthy donors to induce tumor-specific cytotoxic T lymphocytes (CTLs). BDCs expressed significantly higher levels of major histocompatibility complex class I and CD83 in the absence of exogenous stimuli compared with MoDCs. After activation with polyinosinic-polycytidylic acid, BDCs expressed higher levels of major histocompatibility complex class I, CD40, CD80, and CD83, and secreted higher levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8 compared with MoDCs. Despite these differences, both preparations secreted similar levels of IL-12 in response to polyinosinic-polycytidylic acid and, importantly, induced CTL responses of similar magnitude and affinity against influenza matrix protein and MART-1. The ability of BDCs to induce efficient CTL responses, combined with their migratory capacity, makes them an appealing alternative to be investigated in clinical immunotherapy research protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation / metabolism
  • Antigens, Neoplasm / immunology
  • CD11c Antigen / blood
  • CD11c Antigen / immunology*
  • CD40 Ligand / pharmacology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • HLA-DR Antigens / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • MART-1 Antigen
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Neoplasm Proteins / immunology
  • Peptide Fragments / immunology
  • Poly I-C / pharmacology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Toll-Like Receptor 3 / metabolism
  • Viral Matrix Proteins / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Neoplasm
  • CD11c Antigen
  • CMRF-56 antigen
  • Cytokines
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptide Fragments
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Viral Matrix Proteins
  • influenza matrix peptide (58-66)
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma
  • Poly I-C