A simple immunomonitoring procedure for mRNA-loaded dendritic cell therapy

Tumour Biol. 2007;28(6):350-7. doi: 10.1159/000124299. Epub 2008 Apr 4.

Abstract

To develop a simple immunomonitoring method for dendritic cell therapy using messenger RNA (mRNA) as antigen, we evaluated whether Mycobacterium tuberculosis antigen 85A (Ag85A) mRNA-transfected peripheral blood mononuclear cells (PBMCs) could be used to stimulate the induction of interferon (IFN)-gamma-producing T cells. PBMCs from 10 healthy donors were cocultured with autologous PBMCs transfected with mRNA overnight, and the number of IFN-gamma-producing T cells was measured by flow cytometry. IFN-gamma-producing CD4+ and CD8+ T cells were detected in 4 and 5 donors, respectively. PBMCs from 3 donors with negative results were then cocultured with Ag85A mRNA-transfected autologous PBMCs for 1 week to achieve in vitro primary induction of Ag85A-specific T cells. After restimulation with freshly prepared stimulator cells, a small but significant number of IFN-gamma-producing CD8+ T cells was detected. The induction of IFN-gamma-producing CD8+ T cells by overnight coculture was completely abolished by anti-class II or anti-interleukin-12 antibodies, whereas it was partially inhibited by anti-class I antibody. These data suggest that Ag85A mRNA-transfected PBMCs induce specific IFN-gamma-producing T cells and might be applicable for immunomonitoring of mRNA-loaded dendritic cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics*
  • Antigens, Bacterial / genetics*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Coculture Techniques
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • HLA-A Antigens / metabolism
  • HLA-B Antigens / metabolism
  • Humans
  • Interferon-gamma / metabolism*
  • Leukocytes, Mononuclear / metabolism*
  • Lymphocyte Activation
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Tests
  • Transfection
  • Tuberculin Test

Substances

  • Antigens, Bacterial
  • HLA-A Antigens
  • HLA-B Antigens
  • RNA, Messenger
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Interferon-gamma
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis