CpG-oligodeoxynucleotides Co-Stimulate Primary T Cells in the Absence of Antigen-Presenting Cells

Eur J Immunol. 1999 Apr;29(4):1209-18. doi: 10.1002/(SICI)1521-4141(199904)29:04<1209::AID-IMMU1209>3.0.CO;2-J.

Abstract

CpG-containing oligodeoxynucleotides (CpG-ODN) act as powerful adjuvant during in vivo induction of T cell responses. While CpG-ODN directly activate antigen-presenting cells (APC) and thus exert an extrinsic activity on T cells, it is unclear whether they directly affect T cells (intrinsic activity). Here we analyze the effects of CpG-ODN on T cells in an APC-free cell culture. We report that CpG-ODN co-stimulate T cells provided they were triggered via their TCR. CpG-ODN induced IL-2 production, IL-2 receptor expression and thus proliferation. Proliferation was blocked by cyclosporin A or anti-IL-2 monoclonal antibodies (mAb) but not by anti-IL-4 mAb. Moreover, CpG-co-stimulated T cells differentiated into cytolytic T lymphocytes in vitro. Of note, IL-2-driven growth of primed T cells was not affected by CpG-ODN. Co-stimulation was also operative in T cells from CD28-/- mice and in TCR-transgenic T cells stimulated with peptide. CpG-ODN-mediated co-stimulation of T cells in vitro may thus explain part of the potent adjuvant effects of CpG-ODN in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigen-Presenting Cells / physiology*
  • CD28 Antigens / physiology
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Dinucleoside Phosphates / pharmacology*
  • Female
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides / pharmacology*
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Adjuvants, Immunologic
  • CD28 Antigens
  • Dinucleoside Phosphates
  • Interleukin-2
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, T-Cell
  • cytidylyl-3'-5'-guanosine
  • Cyclosporine