CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA

Rachel Flynn, Tarun Hutchinson, Kenneth M. Murphy, Carl F. Ware, Michael Croft, Shahram Salek-Ardakani

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Defining the molecular interactions required to program activated CD8 T cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. HVEM (herpes virus entry mediator) is a member of the tumor necrosis factor receptor (TNFR) family that interacts with ligands in the TNF family, LIGHT and Lymphotoxin-α, and in the Ig family, B and T lymphocyte attenuator (BTLA) and CD160. The Ig family members initiate inhibitory signaling when engaged with HVEM, but may also activate survival gene expression. Using a model of vaccinia virus infection, we made the unexpected finding that deficiency in HVEM or BTLA profoundly impaired effector CD8 T cell survival and development of protective immune memory. Mixed adoptive transfer experiments indicated that BTLA expressed in CD8α+ dendritic cells functions as a trans-activating ligand that delivers positive co-signals through HVEM expressed in T cells. Our data demonstrate a critical role of HVEM-BTLA bidirectional cosignaling system in antiviral defenses by driving the differentiation of memory CD8 T cells.

Original languageEnglish
Pages (from-to)e77991
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint Dive into the research topics of 'CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA'. Together they form a unique fingerprint.

  • Cite this