CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator

Nat Immunol. 2008 Feb;9(2):176-85. doi: 10.1038/ni1554. Epub 2008 Jan 13.


CD160, a glycosylphosphatidylinositol-anchored member of the immunoglobulin superfamily, is expressed on both cytolytic lymphocytes and some unstimulated CD4+ T cells. Here we show that CD160 expression was increased after activation of human CD4+ T cells and that crosslinking CD160 with monoclonal antibody strongly inhibited CD3- and CD28-mediated activation. We found that herpesvirus entry mediator (HVEM) was a ligand of CD160 that acted as a 'bidirectional switch' for T cell activation, producing a positive or negative outcome depending on the engagement of HVEM by CD160 and known HVEM ligands such as B and T lymphocyte attenuator (BTLA) and the T lymphocyte receptor LIGHT. Inhibition of CD4+ T cell activation by HVEM-transfected cells was dependent on CD160 and BTLA; when the cysteine-rich domain 1 of HVEM was deleted, this inhibition was lost, resulting in strong T cell activation. CD160 thus serves as a negative regulator of CD4+ T cell activation through its interaction with HVEM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / metabolism*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cloning, Molecular
  • GPI-Linked Proteins
  • Humans
  • Ligands
  • Lymphocyte Activation* / drug effects
  • Protein Structure, Tertiary
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 14 / genetics
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism*


  • Antibodies, Monoclonal
  • Antigens, CD
  • CD160 protein, human
  • GPI-Linked Proteins
  • Ligands
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor, Member 14