The role of CD200 in immunity to B cell lymphoma

J Leukoc Biol. 2010 Aug;88(2):361-72. doi: 10.1189/jlb.1009686. Epub 2010 May 4.

Abstract

CD200 is a transmembrane protein broadly expressed on a variety of cell types, which delivers immunoregulatory signals through binding to receptors (CD200Rs) expressed on monocytes/myeloid cells and T lymphocytes. Signals delivered through the CD200:CD200R axis have been shown to play an important role in the regulation of anti-tumor immunity, and overexpression of CD200 has been reported in a number of malignancies, including CLL, as well as on cancer stem cells. We investigated the effect of CD200 blockade in vitro on a generation of CTL responses against a poorly immunogenic CD200+ lymphoma cell line and fresh cells obtained from CLL patients using anti-CD200 mAb and CD200-specific siRNAs. Suppression of functional expression of CD200 augmented killing of the CD200+ cells, as well as production of the inflammatory cytokines IFN-gamma and TNF-alpha by effector PBMCs. Killing was mediated by CD8+ cytotoxic T cells, and CD4+ T cells play an important role in CD200-mediated suppression of CTL responses. Our data suggest that CD200 blockade may represent a novel approach to clinical treatment of CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / drug effects
  • Antigens, CD / immunology*
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity*
  • Lymphoma, B-Cell / immunology*
  • RNA, Small Interfering / pharmacology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Cytokines
  • RNA, Small Interfering
  • antigens, CD200