CD8 T Cell Memory to a Viral Pathogen Requires Trans Cosignaling between HVEM and BTLA

نویسندگان

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

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.

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013