HVEM regulates effector versus memory cell fate decisions following respiratory poxvirus infection Academic Article uri icon


  • Abstract During an acute respiratory viral infection, effector CD8 T cells differentiate into short-lived effector cells (SLECs) that are destined to die and memory precursor effector cells (MPECs) that give rise to long-lived memory cells. Defining the precise molecular cues that regulate the survival of MPECs is of great interest. HVEM (Herpes Virus Entry Mediator) is a member of tumor necrosis factor receptor (TNF) superfamily that acts as a molecular switch between pro-inflammatory and inhibitory signaling by respectively binding with its endogenous ligand (LIGHT) from the TNF family and with (BTLA) from the Ig like CD28/B7 family. Using respiratory vaccinia virus (VACV) infection in mice, we found that HVEM was selectively expressed on MPECs but not on SLECs. Lack of HVEM on Ag-specific CD8 T cells resulted in an altered SLEC/MPEC ratio, with effector cells skewing more towards SLEC phenotype. Adoptive transfer of HVEM-deficient MPECs showed markedly increased contraction after viral clearance, leading to nearly complete loss of lung-resident CD8 memory T cells. Similar to CD8 T cells lacking HVEM, WT CD8 T cells failed to accumulate in LIGHT-deficient host but not BTLA-deficient host upon VACV infection. Collectively, these results reveal that HVEM expression on MPECs is critical for the development of long-lived memory cells and suggests that strategies targeting HVEM signaling might be beneficial in augmenting CD8 T cell immunity against respiratory viruses.

published proceedings

  • The Journal of Immunology

author list (cited authors)

  • Desai, P., Abboud, G., Dastmalchi, F., Stanfield, J., Ware, C. F., Croft, M., ... Salek-Ardakani, S.

citation count

  • 0

complete list of authors

  • Desai, Pritesh||Abboud, Georges||Dastmalchi, Farhad||Stanfield, Jessica||Ware, Carl F||Croft, Michael||Song, Jianxun||Hutchinson, Tarun E||Salek-Ardakani, Shahram

publication date

  • May 2016