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

P Soroosh, TA Doherty, T So, AK Mehta… - Journal of Experimental …, 2011 - rupress.org
P Soroosh, TA Doherty, T So, AK Mehta, N Khorram, PS Norris, S Scheu, K Pfeffer, C Ware…
Journal of Experimental Medicine, 2011rupress.org
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 …
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.
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