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Interaction of herpes virus entry mediator (HVEM, CD270, TNFRSF14) with multiple ligands has been proposed to promote or inhibit T\u2010cell responses and inflammation, dependent on the context. In this study, we show that absence of HVEM did neither affect generation of effector nor maintenance of memory antiviral T cells and accordingly viral clearance upon acute and chronic lymphocytic choriomeningitis virus (LCMV) infection, due to potent HVEM downregulation during infection. Notably, overexpression of HVEM on virus\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells resulted in a reduction of effector cells, whereas numbers of memory cells were increased. Overall, this study indicates that downregulation of HVEM driven by LCMV infection ensures an efficient acute response at the price of impaired formation of T\u2010cell memory.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048569","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T11:07:56Z","timestamp":1648465676000},"page":"924-935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LCMV induced downregulation of HVEM on antiviral T\u00a0cells is critical for an efficient effector response"],"prefix":"10.1002","volume":"52","author":[{"given":"Patrizia","family":"Diethelm","sequence":"first","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwana","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-2863","authenticated-orcid":false,"given":"Irina","family":"Iten","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-5202","authenticated-orcid":false,"given":"Jan","family":"Kisielow","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-461X","authenticated-orcid":false,"given":"Mai","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-7140","authenticated-orcid":false,"given":"Manfred","family":"Kopf","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine Institute of Molecular Health Sciences Department of Biology ETH Zurich  Zurich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2251"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90161-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.4049\/jimmunol.157.2.636","article-title":"CD28 costimulation prevents cell death during primary T cell activation","volume":"157","author":"Noel P. 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