Bachy, Emmanuel ORCID: 0000-0003-2694-7510, Urb, Mirjam, Chandra, Shilpi, Robinot, Remy, Bricard, Gabriel, de Bernard, Simon, Traverse-Glehen, Alexandra, Gazzo, Sophie, Blond, Olivier, Khurana, Archana, Baseggio, Lucile, Heavican, Tayla, Ffrench, Martine, Crispatzu, Giuliano, Mondiere, Paul, Schrader, Alexandra, Taillardet, Morgan, Thaunat, Olivier ORCID: 0000-0002-3648-8963, Martin, Nadine, Dalle, Stephane ORCID: 0000-0002-3423-4548, Le Garff-Tavernier, Magali ORCID: 0000-0002-3131-3240, Salles, Gilles, Lachuer, Joel, Hermine, Olivier ORCID: 0000-0003-2574-3874, Asnafi, Vahid, Roussel, Mikael ORCID: 0000-0002-9741-0668, Lamy, Thierry, Herling, Marco, Iqbal, Javeed, Buffat, Laurent, Marche, Patrice N., Gaulard, Philippe, Kronenberg, Mitchell ORCID: 0000-0001-6318-6445, Defrance, Thierry and Genestier, Laurent ORCID: 0000-0002-0527-4583 (2016). CD1d-restricted peripheral T cell lymphoma in mice and humans. J. Exp. Med., 213 (5). S. 841 - 858. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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Abstract

Peripheral T cell lymphomas ( PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within V delta 1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bachy, EmmanuelUNSPECIFIEDorcid.org/0000-0003-2694-7510UNSPECIFIED
Urb, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chandra, ShilpiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinot, RemyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bricard, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Bernard, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Traverse-Glehen, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gazzo, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blond, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khurana, ArchanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baseggio, LucileUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heavican, TaylaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ffrench, MartineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crispatzu, GiulianoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mondiere, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schrader, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taillardet, MorganUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thaunat, OlivierUNSPECIFIEDorcid.org/0000-0002-3648-8963UNSPECIFIED
Martin, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dalle, StephaneUNSPECIFIEDorcid.org/0000-0002-3423-4548UNSPECIFIED
Le Garff-Tavernier, MagaliUNSPECIFIEDorcid.org/0000-0002-3131-3240UNSPECIFIED
Salles, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lachuer, JoelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermine, OlivierUNSPECIFIEDorcid.org/0000-0003-2574-3874UNSPECIFIED
Asnafi, VahidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roussel, MikaelUNSPECIFIEDorcid.org/0000-0002-9741-0668UNSPECIFIED
Lamy, ThierryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iqbal, JaveedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buffat, LaurentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marche, Patrice N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaulard, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kronenberg, MitchellUNSPECIFIEDorcid.org/0000-0001-6318-6445UNSPECIFIED
Defrance, ThierryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genestier, LaurentUNSPECIFIEDorcid.org/0000-0002-0527-4583UNSPECIFIED
URN: urn:nbn:de:hbz:38-276022
DOI: 10.1084/jem.20150794
Journal or Publication Title: J. Exp. Med.
Volume: 213
Number: 5
Page Range: S. 841 - 858
Date: 2016
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-9538
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NKT CELLS; GENE-EXPRESSION; SEZARY-SYNDROME; B-CELL; CYTOKINE PRODUCTION; TCR; MUTATIONS; ANTIGENS; GAMMA; INFECTIONMultiple languages
Immunology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27602

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