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© Charles DAUGUET, Institut Pasteur
HIV particles
Publication : The Journal of experimental medicine

CD1d-restricted peripheral T cell lymphoma in mice and humans.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of experimental medicine - 02 May 2016

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,

Link to Pubmed [PMID] – 27069116

Link to DOI – 10.1084/jem.20150794

J Exp Med 2016 05; 213(5): 841-57

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 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.

https://pubmed.ncbi.nlm.nih.gov/27069116