The PPARα pathway in Vγ9Vδ2 T cell anergy

authors

• 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

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.

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