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

Blood. 2002 Aug 1;100(3):1019-25. doi: 10.1182/blood-2001-12-0303.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, CD / pharmacology*
  • Apoptosis / drug effects
  • CD3 Complex / physiology*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukocyte Immunoglobulin-like Receptor B1
  • Lymphocyte Activation
  • Lymphoma, T-Cell, Cutaneous / enzymology
  • Lymphoma, T-Cell, Cutaneous / metabolism
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / metabolism
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR3DL2
  • Sezary Syndrome / diagnosis
  • Sezary Syndrome / metabolism
  • Sezary Syndrome / pathology*
  • Signal Transduction / drug effects*

Substances

  • Antigens, CD
  • CD3 Complex
  • Intracellular Signaling Peptides and Proteins
  • KIR2DL2 protein, human
  • KIR3DL2 protein, human
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR3DL2
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases