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Journal Articles Journal of Experimental Medicine Year : 2016

CD1d-restricted peripheral T cell lymphoma in mice and humans

Simon de Bernard
  • Function : Author
Laurent Buffat
  • Function : Author


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-killedStreptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereasEscherichia coliinjection 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

Dates and versions

hal-01305487 , version 1 (21-04-2016)



Emmanuel Bachy, Mirjam Urb, Shilpi Chandra, Rémy Robinot, Gabriel Bricard, et al.. CD1d-restricted peripheral T cell lymphoma in mice and humans. Journal of Experimental Medicine, 2016, 213 (5), pp.841-57. ⟨10.1084/jem.20150794⟩. ⟨hal-01305487⟩
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