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

Abstract:

: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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Cai G,Anumanthan A,Brown JA,Greenfield EA,Zhu B,Freeman GJ

doi

10.1038/ni1554

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

176-85

issue

2

eissn

1529-2908

issn

1529-2916

pii

ni1554

journal_volume

9

pub_type

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