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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-12-0303.

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Blood, 1 August 2002, Vol. 100, No. 3, pp. 1019-1025

NEOPLASIA

Engagement of ILT2/CD85j in Sézary syndrome cells inhibits their CD3/TCR signaling

Maria Nikolova, Philippe Musette, Martine Bagot, Laurence Boumsell, and Armand Bensussan

From INSERM 448 and Dermatology Department, Faculté de Médecine de Créteil, Créteil, France, and INSERM 532, Institut de Recherche sur la Peau, Paris, France.

Extensive phenotype analysis of cutaneous T-cell lymphoma (CTCL) malignant cell lines revealed surface expression of receptors usually not detected on normal circulating CD4+CD45RO+ lymphocytes. We previously found that CTCL malignant cells express the killer cell immunoglobulinlike receptor (KIR) KIR3DL2/CD158k, whereas they fail to express the other KIRs. In the present study, we report for the first time that the CD85j/immunoglobulin (Ig)-like transcript 2 (ILT2) receptor is found on Sézary cell lines and on circulating Sézary malignant CD4+ cells, while it is hardly detectable on circulating CD4+ lymphocytes from healthy individuals. We demonstrate that ILT2 is functional on CTCL cells, as its triggering leads to the recruitment of Src homology 2 domain-containing tyrosine phosphatase (SHP-1) and to the specific inhibition of CTCL malignant cell proliferation induced by CD3/T-cell receptor (TCR) stimulation. Interestingly, we found that separated CD4+ILT2+ circulating malignant Sézary cells are less susceptible to anti-CD3 monoclonal antibody (mAb)-induced cell death than autologous CD4+ILT2- lymphocytes. Therefore, the resistance to apoptosis of Sézary cells may result from distinct mechanisms including cytokine-induced high levels of bcl-2 and specific expression of inhibitory receptors involved in lymphocyte survival.

© 2002 by The American Society of Hematology.
 

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