CpG-oligodeoxynucleotides Enhance T-cell Receptor-Triggered Interferon-Gamma Production and Up-Regulation of CD69 via Induction of Antigen-Presenting Cell-Derived Interferon Type I and interleukin-12

Immunology. 2000 Feb;99(2):170-8. doi: 10.1046/j.1365-2567.2000.00964.x.

Abstract

Bacterial cytidine-phosphate-guanosine (CpG-DNA) activates antigen-presenting cells (APC) and drives T helper 1 (Th1)-polarized immune responses in the mouse. Claims have been made that CpG-DNA costimulates murine T cells. We examined the direct and indirect effects of CpG-oligodeoxynucleotides (CpG-ODN) on human T-cell activation. CpG-ODN failed to costimulate purified human T cells activated with alpha-CD3 or alpha-T-cell receptor (TCR)alphabeta antibodies. In contrast, CpG-ODN sequence-specifically caused increased expression of CD69 on CD4 and CD8 T cells when peripheral blood mononuclear cells (PBMC) were stimulated via alpha-CD3. CpG-ODN and alpha-CD3 stimulation synergized to induce interferon-gamma (IFN-gamma) in T cells and natural killer (NK) cells, as shown by intracellular fluorescence-activated cell sorter (FACS) staining. These effects of CpG-ODN on human T cells were caused by the release of IFN type I (IFN-I) and interleukin-12 (IL-12) from PBMC. Enhancement of CD69 expression on alpha-CD3-triggered T cells could be reproduced in a coculture transwell system of purified T cells and PBMC, was inhibited by neutralizing antibodies to IFN-I and could be mimicked by adding exogenous IFN-I. Furthermore, neutralization of either IFN-I or IL-12 diminished, and in combination abolished, IFN-gamma production. These findings show that CpG-ODN potentiate TCR-triggered activation of human T cells in an APC-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD3 Complex / immunology
  • Cell Culture Techniques
  • CpG Islands / immunology*
  • Cytokines / immunology*
  • Humans
  • Interferon Type I / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology
  • Lectins, C-Type
  • Lymphocyte Activation / immunology*
  • Oligodeoxyribonucleotides / immunology*
  • T-Lymphocytes / immunology*
  • Up-Regulation

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Cytokines
  • Interferon Type I
  • Lectins, C-Type
  • Oligodeoxyribonucleotides
  • Interleukin-12
  • Interferon-gamma