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

9 Scopus citations

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

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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., ... 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