Open Access

The PPARα pathway in Vγ9Vδ2 T cell anergy

  • Mary Poupot1, 2, 3Email author,
  • Frédéric Boissard1, 2, 3,
  • Delphine Betous1, 2, 3,
  • Laure Bardouillet4,
  • Séverine Fruchon5,
  • Fatima L’Faqihi-Olive5,
  • Frédéric Pont1,
  • Mourad Mekaouche4,
  • Sophie Ingoure6,
  • Hélène Sicard6,
  • Guy Dubreuilh4 and
  • Jean-Jacques Fournié1, 2, 3
Cellular & Molecular Biology LettersAn International Journal201419:218

https://doi.org/10.2478/s11658-014-0218-0

Received: 19 June 2014

Accepted: 30 October 2014

Published: 25 November 2014

Abstract

Phosphoantigens (PAgs) activate Vγ9Vδ2 T lymphocytes, inducing their potent and rapid response in vitro and in vivo. However, humans and nonhuman primates that receive repeated injections of PAgs progressively lose their Vγ9Vδ2 T cell response to them. To elucidate the molecular mechanisms of this in vivo desensitization, we analyzed the transcriptome of circulating Vγ9Vδ2 T cells from macaques injected with PAg. We showed that three PAg injections induced the activation of the PPARα pathway in Vγ9Vδ2 T cells. Thus, we analyzed the in vitro response of Vγ9Vδ2 T cells stimulated with a PPARα agonist. We demonstrated that in vitro PPARα pathway activation led to the inhibition of the BrHPP-induced activation and proliferation of human Vγ9Vδ2 T cells. Since the PPARα pathway is involved in the antigen-selective desensitization of human Vγ9Vδ2 T cells, the use of PPARα inhibitors could enhance cancer immunotherapy based on Vγ9Vδ2 T cells.

Keywords

ActivationGamma-delta T-lymphocyteImmunotherapyPhosphoantigenTCRPPARα

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