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Rôle des nectines dans la reconnaissance des cellules tumorales par les lymphocytes T yδ

Abstract : T cells that express a γδ TCR (γδ T cells) are T cells that recognize non-conventional antigens independently of the MHC (major histocompatibility complex). In humans, the Vγ9Vδ2 T subpopulation that is predominant in the peripheral blood plays an important role in the anti-tumor immunity. Vγ9Vδ2 T cells recognize tumor cells through their TCR and/or their NK receptors. The work was focused on one of these receptors CRTAM and the role of its interaction with its ligand Necl-2 expressed by tumor cells. We show that CRTAM is transiently expressed in activated Vγ9Vδ2 T cells. To study the interaction of CRTAM with its ligand Necl-2, we developed models of tumor cells expressing Necl-2 after retroviral transduction. We observed that the interaction of Vγ9Vδ2 T cells with Necl-2+ tumor cells leaded to a reduction of CRTAM expression to the surface of lymphocytes. Concomitantly, Necl-2+ tumor cells acquire CRTAM through a trogocytosis mechanism. Unlike CD8 T cells and NK cells, we did not observe any impact of the CRTAM/Necl-2 interaction on the cytotoxicity and IFN-γ secretion of Vγ9Vδ2 T cells. On the other side, this interaction leads to the death of Vγ9Vδ2 T cells by a mechanism of autophagy. Our results suggest that the expression of Necl-2 by tumor cells would allow them to escape Vγ9Vδ2 T cell response.
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https://tel.archives-ouvertes.fr/tel-00795222
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Submitted on : Wednesday, February 27, 2013 - 3:53:15 PM
Last modification on : Wednesday, March 30, 2022 - 2:35:22 PM
Long-term archiving on: : Tuesday, May 28, 2013 - 7:00:09 AM

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  • HAL Id : tel-00795222, version 1

Citation

Benoît Dessarthe. Rôle des nectines dans la reconnaissance des cellules tumorales par les lymphocytes T yδ. Cancer. Université Rennes 1, 2012. Français. ⟨tel-00795222⟩

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