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* Laboratoire "Immunologie des tumeurs humaines: Interaction effecteurs cytotoxiques-système tumoral," Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 753, Institut Fédératif de Recherche (IFR) 54, Institut Gustave Roussy (IGR), Villejuif, France;
Unité de Génomique Fonctionnelle, IFR 54, IGR, Villejuif, France;
Département de Biologie Clinique, IGR, Villejuif, France;
Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8126, IGR, Villejuif, France;
¶ Faculty of Medicine, INSERM Unité 448, Créteil, France; and
|| INSERM Unité 567, CNRS UMR 8104, Institut Cochin, Département de Biologie Cellulaire, Laboratoire labellisé par la Ligue Nationale contre le Cancer, Université René Descartes, Paris, France
We previously characterized several tumor-specific T cell clones from PBL and tumor-infiltrating lymphocytes of a lung cancer patient with identical TCR rearrangements and similar lytic potential, but with different antitumor response. A role of the TCR inhibitory molecule CD5 to impair reactivity of peripheral T cells against the tumor was found to be involved in this process. In this report, we demonstrate that CD5 also controls the susceptibility of specific T cells to activation-induced cell death (AICD) triggered by the tumor. Using a panel of tumor-infiltrating lymphocytes and PBL-derived clones expressing different levels of CD5, our results indicate that T lymphocyte AICD in response to the cognate tumor is inversely proportional to the surface expression level of CD5. They also suggest a direct involvement of CD5 in this process, as revealed by an increase in tumor-mediated T lymphocyte AICD following neutralization of the molecule with specific mAb. Mechanistically, our data indicate that down-regulation of FasL expression and subsequent inhibition of caspase-8 activation are involved in CD5-induced T cell survival. These results provide evidence for a role of CD5 in the fate of peripheral tumor-specific T cells and further suggest its contribution to regulate the extension of CTL response against tumor.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer (ARC; Grants 3810 and 3501), the Ligue Contre le Cancer (Comité Val de Marne), the Cancéropôle Ile de France, and the Institut National du Cancer. G.F. was supported by a fellowship from Marie Curie; F.E.H. was supported by a fellowship from the ARC.
2 G.F. and F.E.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Fathia Mami-Chouaib, Laboratory "Immunologie des tumeurs humaines: Interaction effecteurs cytotoxiques-système tumoral," Institut National de la Santé et de la Recherche Médicale Unité 753, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France. E-mail address: cfathia{at}igr.fr
4 Abbreviations used in this paper: AICD, activation-induced cell death; TIL, tumor-infiltrating lymphocyte; PI, propidium iodide; DISC, death-inducing signaling complex; c-FLIP, cellular FLIP.
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