Herpesvirus entry mediator (TNFRSF14) regulates the persistence of T helper memory cell populations

Pejman Soroosh, Taylor A. Doherty, Takanori So, Amit Kumar Mehta, Naseem Khorram, Paula S. Norris, Stefanie Scheu, Klaus Pfeffer, Carl Ware, Michael Croft

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Memory T helper cells (Th cells) play an important role in host defense against pathogens but also contribute to the pathogenesis of inflammatory disorders. We found that a soluble decoy lymphotoxin β receptor (LT-βR)-Fc, which can block tumor necrosis factor (TNF)-related ligands LIGHT (TNFSF14) and LT-αβ binding to the herpesvirus entry mediator (HVEM) and the LT-βR, inhibited the accumulation of memory Th2 cells after antigen encounter and correspondingly reduced inflammatory responses in vivo. Showing that this was a function of the receptor for LIGHT, antigen-specific memory CD4 T cells deficient in HVEM were also unable to persist, despite having a normal immediate response to recall antigen. HVEM-/- memory Th2 cells displayed reduced activity of PKB (protein kinase B; Akt), and constitutively active Akt rescued their survival and restored strong inflammation after antigen rechallenge. This was not restricted to Th2 memory cells as HVEM-deficient Th1 memory cells were also impaired in surviving after encounter with recall antigen. Furthermore, the absence of LIGHT on T cells recapitulated the defect seen with the absence of HVEM, suggesting that activated T cells communicate through LIGHT-HVEM interactions. Collectively, our results demonstrate a critical role of HVEM signals in the persistence of large pools of memory CD4 T cells.

Original languageEnglish
Pages (from-to)797-809
Number of pages13
JournalJournal of Experimental Medicine
Volume208
Issue number4
DOIs
Publication statusPublished - 2011 Apr 11

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Soroosh, P., Doherty, T. A., So, T., Mehta, A. K., Khorram, N., Norris, P. S., Scheu, S., Pfeffer, K., Ware, C., & Croft, M. (2011). Herpesvirus entry mediator (TNFRSF14) regulates the persistence of T helper memory cell populations. Journal of Experimental Medicine, 208(4), 797-809. https://doi.org/10.1084/jem.20101562