Generation of activated and antigen-specific T cells with cytotoxic activity after co-culture with dendritic cells

Cancer Immunol Immunother. 2002 Mar;51(1):25-32. doi: 10.1007/s00262-001-0251-5. Epub 2001 Dec 21.

Abstract

Co-culturing of immunological effector cells with antigen-pulsed DC leads to an increase of cytotoxic activity against antigen-expressing tumour cells. Using this approach, we could detect up to 2.8% antigen-specific CTLs after co-culture with antigen-pulsed DC. However, the required high effector cell numbers remain a major obstacle in immunotherapy. In this study, we show an approach for generating activated and antigen-specific effector cells that enables us to decrease effector to target cell ratios. We used an interferon-gamma secretion assay to enrich activated effector cells after co-culture with antigen-pulsed dendritic cells (DC). Purified immunological effector cells lysed 58.3% of antigen-expressing tumour cells at an effector to target ratio of 1:1. Furthermore, using MHC-IgG complexes, we enriched effector cells expressing antigen-specific T-cell receptor after co-culture with DC. Performing ELISpot, flow cytometry and TCR analysis, we could show a significant increase of activated and specific TCR-expressing effector cells after co-culture with DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Carcinoembryonic Antigen / chemistry
  • Carcinoembryonic Antigen / immunology*
  • Cells, Cultured / immunology
  • Cells, Cultured / metabolism
  • Coculture Techniques
  • Colonic Neoplasms / pathology
  • Dendritic Cells / immunology*
  • Dimerization
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tumor Cells, Cultured / immunology

Substances

  • Antigens, Neoplasm
  • Carcinoembryonic Antigen
  • HLA-A2 Antigen
  • Immunoglobulin G
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Interferon-gamma