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Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance
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Published on: July 22, 2011

Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO

Gerhard Wingender1, Natalio Garbi, Beatrix Schumak

  • 1Institut für Molekulare Medizin und Experimentelle Immunologie, Bonn, Germany.

European Journal of Immunology
|December 3, 2005
PubMed

Insights

CpG oligonucleotides (CpG-ODN) can stimulate or suppress immune responses. Application site determines the effect: subcutaneous boosts immunity, while systemic application suppresses T cell activity via indoleamine 2,3-dioxygenase (IDO).

Area of Science:

  • Immunology
  • Vaccinology

Background:

  • CpG-rich oligonucleotides (CpG-ODN) are known Toll-like receptor 9 (TLR9) agonists used as vaccine adjuvants.
  • Their immune-modulating effects are typically considered stimulatory.

Purpose of the Study:

  • To investigate the dual role of CpG-ODN as immune stimulators and suppressors.
  • To determine the influence of anatomical application site on CpG-ODN's immune effects.
  • To elucidate the mechanism underlying CpG-ODN-induced immune suppression.

Main Methods:

  • Administered antigen plus CpG-ODN subcutaneously and systemically in mice.
  • Assessed antigen-specific T cell activation in lymph nodes and spleen.
  • Measured CTL activity.
  • Investigated the role of indoleamine 2,3-dioxygenase (IDO) using 1-methyl-tryptophan (1-MT).
  • Utilized knockout mice lacking TLR9, type I, and type II interferons.

Main Results:

  • Subcutaneous application of CpG-ODN with antigen led to T cell activation in local lymph nodes.
  • Systemic application of CpG-ODN resulted in suppressed T cell expansion and CTL activity in the spleen.
  • CpG-ODN induced IDO expression in the spleen, and 1-MT abrogated the T cell suppression.
  • IDO expression was not observed in lymph nodes.
  • CpG-ODN-induced suppression was TLR9-dependent but independent of type I and II interferons.

Conclusions:

  • The route of administration is critical for the immune outcome of CpG-ODN application.
  • Systemic CpG-ODN can induce immune suppression mediated by IDO, primarily in the spleen.
  • CpG-ODN's potential for immune suppression could be harnessed for treating certain pathological conditions.

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