{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:25Z","timestamp":1792788385866,"version":"4.5.0"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,4,6]]},"abstract":"<jats:p>The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxides. Although Gpx4 represents a key component of the reactive oxygen species-scavenging network, its relevance in the immune system is yet to be defined. Here, we investigated the importance of Gpx4 for physiological T cell responses by using T cell\u2013specific Gpx4-deficient mice. Our results revealed that, despite normal thymic T cell development, CD8+ T cells from T\u0394Gpx4\/\u0394Gpx4 mice had an intrinsic defect in maintaining homeostatic balance in the periphery. Moreover, both antigen-specific CD8+ and CD4+ T cells lacking Gpx4 failed to expand and to protect from acute lymphocytic choriomeningitis virus and Leishmania major parasite infections, which were rescued with diet supplementation of high dosage of vitamin E. Notably, depletion of the Gpx4 gene in the memory phase of viral infection did not affect T cell recall responses upon secondary infection. Ex vivo, Gpx4-deficient T cells rapidly accumulated membrane lipid peroxides and concomitantly underwent cell death driven by ferroptosis but not necroptosis. These studies unveil an essential role of Gpx4 for T cell immunity.<\/jats:p>","DOI":"10.1084\/jem.20140857","type":"journal-article","created":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T09:30:53Z","timestamp":1427794253000},"page":"555-568","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":651,"title":["T cell lipid peroxidation induces ferroptosis and prevents immunity to infection"],"prefix":"10.1084","volume":"212","author":[{"given":"Mai","family":"Matsushita","sequence":"first","affiliation":[{"name":"Molecular Biomedicine, Institute of Molecular Health Science, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Freigang","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine, Institute of Molecular Health Science, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schneider","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine, Institute of Molecular Health Science, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Conrad","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, Institute of Developmental Genetics, 85764 Neuherberg, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg W.","family":"Bornkamm","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, Institute of Clinical Molecular Biology and Tumor Genetics, 81377 Munich, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Kopf","sequence":"additional","affiliation":[{"name":"Molecular Biomedicine, Institute of Molecular Health Science, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,3,30]]},"reference":[{"key":"2023072602543422900_bib1","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1073\/pnas.022630299","article-title":"Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation","volume":"99","author":"Angelini","year":"2002","journal-title":"Proc. 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