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The PPARα pathway in Vγ9Vδ2 T cell anergy

Cellular & Molecular Biology Letters volume 19, pages 649–658 (2014)Cite this article

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.

Abbreviations

CFSE:

carboxyfluorescein succidimidyl ester

GSEA:

Gene Set Enrichment Analysis

IL-2:

interleukin 2

PAg:

phosphoantigen

PPAR:

peroxisome proliferator-activated receptors

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Authors and Affiliations

  1. INSERM UMR1037-Cancer Research Center of Toulouse, CHU Purpan, F-31300, Toulouse, France

    Mary Poupot, Frédéric Boissard, Delphine Betous, Frédéric Pont & Jean-Jacques Fournié

  2. ERL 5294 CNRS, CHU Purpan, BP3028, F-31300, Toulouse, France

    Mary Poupot, Frédéric Boissard, Delphine Betous & Jean-Jacques Fournié

  3. Université Toulouse III Paul-Sabatier, 31300, Toulouse, France

    Mary Poupot, Frédéric Boissard, Delphine Betous & Jean-Jacques Fournié

  4. Station de Primatologie, UPS 846, Centre National de la Recherche Scientifique, F-13790, Rousset sur Arc, France

    Laure Bardouillet, Mourad Mekaouche & Guy Dubreuilh

  5. INSERM U1043-CPTP Toulouse, F-31300, Toulouse, France

    Séverine Fruchon & Fatima L’Faqihi-Olive

  6. Innate Pharma, F-13276, Marseille, France

    Sophie Ingoure & Hélène Sicard

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  1. Mary Poupot
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  2. Frédéric Boissard
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  12. Jean-Jacques Fournié
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Correspondence to Mary Poupot.

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Poupot, M., Boissard, F., Betous, D. et al. The PPARα pathway in Vγ9Vδ2 T cell anergy. Cell Mol Biol Lett 19, 649–658 (2014). https://doi.org/10.2478/s11658-014-0218-0

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

Keywords

  • Activation
  • Gamma-delta T-lymphocyte
  • Immunotherapy
  • Phosphoantigen
  • TCR
  • PPARα

Cellular & Molecular Biology Letters

ISSN: 1689-1392

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