The PPARα pathway in Vγ9Vδ2 T cell anergy


  • Poupot Mary
  • Boissard Frédéric
  • Bétous Delphine
  • Bardouillet Laure
  • Fruchon Séverine
  • L’faqihi-Olive Fatima-Ezzahra
  • Pont Frédéric
  • Mekaouche Mourad
  • Ingoure Sophie
  • Sicard Helene
  • Dubreuilh Guy
  • Fournié Jean-Jacques


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.

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