title: The PPARα pathway in Vγ9Vδ2 T cell anergy.
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.
authors.affiliation: INSERM UMR1037-Cancer Research Center of Toulouse, CHU Purpan, F-31300, Toulouse, France, mary.poupot@inserm.fr.
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boissard
authors.forename: Delphine
authors.initials: D
authors.lastname: Betous
authors.forename: Laure
authors.initials: L
authors.lastname: Bardouillet
authors.forename: Séverine
authors.initials: S
authors.lastname: Fruchon
authors.forename: Fatima
authors.initials: F
authors.lastname: L'Faqihi-Olive
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pont
authors.forename: Mourad
authors.initials: M
authors.lastname: Mekaouche
authors.forename: Sophie
authors.initials: S
authors.lastname: Ingoure
authors.forename: Hélène
authors.initials: H
authors.lastname: Sicard
authors.forename: Guy
authors.initials: G
authors.lastname: Dubreuilh
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D017635:Clonal Anergy; D006801:Humans; D008252:Macaca fascicularis; D047493:PPAR alpha / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D047493:PPAR alpha