| First Author | Soroosh P | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 4 | Pages | 797-809 |
| PubMed ID | 21402741 | Mgi Jnum | J:176832 |
| Mgi Id | MGI:5292801 | Doi | 10.1084/jem.20101562 |
| Citation | Soroosh P, et al. (2011) Herpesvirus entry mediator (TNFRSF14) regulates the persistence of T helper memory cell populations. J Exp Med 208(4):797-809 |
| abstractText | 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 beta receptor (LT-betaR)-Fc, which can block tumor necrosis factor (TNF)-related ligands LIGHT (TNFSF14) and LT-alphabeta binding to the herpesvirus entry mediator (HVEM) and the LT-betaR, 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. |
