Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells

Biochem Biophys Res Commun. 2006 Jun 16;344(4):1121-7. doi: 10.1016/j.bbrc.2006.03.242. Epub 2006 Apr 21.

Abstract

Co-signal receptors provide crucial activating or attenuating signals for T cells. The B and T lymphocyte attenuator (BTLA/CD272) is a third member of co-inhibitory receptors, which belongs to the CD28 immunoglobulin-superfamily. Using monoclonal antibodies (mAbs) against human BTLA, we show that BTLA is constitutively expressed on most CD4+ and CD8+ T cells and its expression progressively decreases upon T cell activation. Polarized Th1 and Th2 cells contained both BTLA-positive and BTLA-negative populations, but the extended culture diminished BTLA expression. Cross-linking BTLA with an agonistic mAb inhibited T cell proliferation and the production of the cytokines IFN-gamma and IL-10 in response to anti-CD3 stimulation. BTLA-mediated inhibition of T cell activation occurred during both primary CD4+ T cell responses and secondary CD4+ and CD8+ T cell responses, suggesting that BTLA ligation sends a constitutive "off" signal to T cells and thus might play an important role in the maintenance of T cell tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Receptors, Immunologic / agonists
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / metabolism*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Antibodies, Monoclonal
  • BTLA protein, human
  • CD3 Complex
  • Receptors, Immunologic
  • Interleukin-10
  • Interferon-gamma