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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.

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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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