CD1d-restricted peripheral T cell lymphoma in mice and humans

Emmanuel Bachy, Mirjam Urb, Shilpi Chandra, Rémy Robinot, Gabriel Bricard, Simon de Bernard, Alexandra Traverse-Glehen, Sophie Gazzo, Olivier Blond, Archana Khurana, Lucile Baseggio, Tayla Heavican, Martine Ffrench, Giuliano Crispatzu, Paul Mondière, Alexandra Schrader, Morgan Taillardet, Olivier Thaunat, Nadine Martin, Stéphane DalleMagali Le Garff-Tavernier, Gilles Salles, Joel Lachuer, Olivier Hermine, Vahid Asnafi, Mikael Roussel, Thierry Lamy, Marco Herling, Javeed Iqbal, Laurent Buffat, Patrice N. Marche, Philippe Gaulard, Mitchell Kronenberg, Thierry Defrance, Laurent Genestier

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 downregulation 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 Vδ1 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.

Original languageEnglish (US)
Pages (from-to)841-857
Number of pages17
JournalJournal of Experimental Medicine
Volume213
Issue number5
DOIs
StatePublished - Jan 1 2016

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Peripheral T-Cell Lymphoma
Natural Killer T-Cells
Lymphoma
Blocking Antibodies
T-Lymphocytes
Injections
Glycolipids
Streptococcus pneumoniae
Transcriptome
Cyclosporine
Anti-Idiotypic Antibodies
Up-Regulation
Therapeutics
Down-Regulation
Hot Temperature
Escherichia coli
Antigens
Incidence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bachy, E., Urb, M., Chandra, S., Robinot, R., Bricard, G., de Bernard, S., ... Genestier, L. (2016). CD1d-restricted peripheral T cell lymphoma in mice and humans. Journal of Experimental Medicine, 213(5), 841-857. https://doi.org/10.1084/jem.20150794

CD1d-restricted peripheral T cell lymphoma in mice and humans. / Bachy, Emmanuel; Urb, Mirjam; Chandra, Shilpi; Robinot, Rémy; Bricard, Gabriel; de Bernard, Simon; Traverse-Glehen, Alexandra; Gazzo, Sophie; Blond, Olivier; Khurana, Archana; Baseggio, Lucile; Heavican, Tayla; Ffrench, Martine; Crispatzu, Giuliano; Mondière, Paul; Schrader, Alexandra; Taillardet, Morgan; Thaunat, Olivier; Martin, Nadine; Dalle, Stéphane; Le Garff-Tavernier, Magali; Salles, Gilles; Lachuer, Joel; Hermine, Olivier; Asnafi, Vahid; Roussel, Mikael; Lamy, Thierry; Herling, Marco; Iqbal, Javeed; Buffat, Laurent; Marche, Patrice N.; Gaulard, Philippe; Kronenberg, Mitchell; Defrance, Thierry; Genestier, Laurent.

In: Journal of Experimental Medicine, Vol. 213, No. 5, 01.01.2016, p. 841-857.

Research output: Contribution to journalArticle

Bachy, E, Urb, M, Chandra, S, Robinot, R, Bricard, G, de Bernard, S, Traverse-Glehen, A, Gazzo, S, Blond, O, Khurana, A, Baseggio, L, Heavican, T, Ffrench, M, Crispatzu, G, Mondière, P, Schrader, A, Taillardet, M, Thaunat, O, Martin, N, Dalle, S, Le Garff-Tavernier, M, Salles, G, Lachuer, J, Hermine, O, Asnafi, V, Roussel, M, Lamy, T, Herling, M, Iqbal, J, Buffat, L, Marche, PN, Gaulard, P, Kronenberg, M, Defrance, T & Genestier, L 2016, 'CD1d-restricted peripheral T cell lymphoma in mice and humans', Journal of Experimental Medicine, vol. 213, no. 5, pp. 841-857. https://doi.org/10.1084/jem.20150794
Bachy E, Urb M, Chandra S, Robinot R, Bricard G, de Bernard S et al. CD1d-restricted peripheral T cell lymphoma in mice and humans. Journal of Experimental Medicine. 2016 Jan 1;213(5):841-857. https://doi.org/10.1084/jem.20150794
Bachy, Emmanuel ; Urb, Mirjam ; Chandra, Shilpi ; Robinot, Rémy ; Bricard, Gabriel ; de Bernard, Simon ; Traverse-Glehen, Alexandra ; Gazzo, Sophie ; Blond, Olivier ; Khurana, Archana ; Baseggio, Lucile ; Heavican, Tayla ; Ffrench, Martine ; Crispatzu, Giuliano ; Mondière, Paul ; Schrader, Alexandra ; Taillardet, Morgan ; Thaunat, Olivier ; Martin, Nadine ; Dalle, Stéphane ; Le Garff-Tavernier, Magali ; Salles, Gilles ; Lachuer, Joel ; Hermine, Olivier ; Asnafi, Vahid ; Roussel, Mikael ; Lamy, Thierry ; Herling, Marco ; Iqbal, Javeed ; Buffat, Laurent ; Marche, Patrice N. ; Gaulard, Philippe ; Kronenberg, Mitchell ; Defrance, Thierry ; Genestier, Laurent. / CD1d-restricted peripheral T cell lymphoma in mice and humans. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 5. pp. 841-857.
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AU - Bachy, Emmanuel

AU - Urb, Mirjam

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AU - de Bernard, Simon

AU - Traverse-Glehen, Alexandra

AU - Gazzo, Sophie

AU - Blond, Olivier

AU - Khurana, Archana

AU - Baseggio, Lucile

AU - Heavican, Tayla

AU - Ffrench, Martine

AU - Crispatzu, Giuliano

AU - Mondière, Paul

AU - Schrader, Alexandra

AU - Taillardet, Morgan

AU - Thaunat, Olivier

AU - Martin, Nadine

AU - Dalle, Stéphane

AU - Le Garff-Tavernier, Magali

AU - Salles, Gilles

AU - Lachuer, Joel

AU - Hermine, Olivier

AU - Asnafi, Vahid

AU - Roussel, Mikael

AU - Lamy, Thierry

AU - Herling, Marco

AU - Iqbal, Javeed

AU - Buffat, Laurent

AU - Marche, Patrice N.

AU - Gaulard, Philippe

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AU - Defrance, Thierry

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