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- W4313349586 abstract "Abstract Upon activation with phosphoantigens (PAgs), human and non-human primates circulating TCRVγ9Vδ2 T lymphocytes release pro-inflammatory cytokines, mediate tumor cell cytotoxicity and proliferate through an IL2-dependent clonal expansion. Together, these features make it versatile and attractive candidates for new cancer immunotherapies (Kabelitz, D et al., 2007, Canc.Res., 67(1):5-8). Despite a potent and rapid response of the TCRVγ9Vδ2 T lymphocytes in vitro and in vivo, repeated stimulations with PAgs desensitize selectively this T cell lineage in humans and non-human primates (Cendron, D. et al., 2007, Eur.J.Immunol., 37(2):549-65; Sicard, H. et al., 2005, J.Immunol., 175(8):5471-80). Thus, we investigated the gene expression pattern associated with this PAg-selective anergy of these lymphocytes. TCRVγ9Vδ2 T cells were isolated from blood samples from PAgs-injected macaques (3 repeated injections) for transcriptome studies. After the third stimulation, in addition to some genes corresponding to the inhibition of cell cycle, a significant gene signature emerged from the desensitized γδ T cells transcriptome involving the PPARα and CARM1 pathways, based on up-regulation of both EP300, HSD17B4, PRKAR2B and RB1 genes while RARA and PRKCA (PKCα) were down-regulated. Moreover, inhibition of proliferation and cytokine production by PPARα agonists-treated human TCRVγ9Vδ2 T lymphocytes confirmed the implication of PPARα pathway in the γδ T cells desensitization by PAgs." @default.
- W4313349586 created "2023-01-06" @default.
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- W4313349586 date "2013-05-01" @default.
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- W4313349586 title "Molecular mechanism of the Vγ9Vδ2 T lymphocytes anergy. (P4385)" @default.
- W4313349586 doi "https://doi.org/10.4049/jimmunol.190.supp.205.2" @default.
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