{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T16:15:20Z","timestamp":1757780120032},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T00:00:00Z","timestamp":1339113600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,6]]},"abstract":"Perforin\u2010deficient (PKO<\/jats:styled-content>) mice serve as models for familial hemophagocytic lympho\u2010histiocytosis, a uniformly fatal disease associated with viral infection of perforin\u2010deficient humans. Na\u00efve perforin\u2010deficient BALB<\/jats:styled-content>\/c mice survive while vaccinated PKO<\/jats:styled-content> mice containing virus\u2010specific memory CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content> cells rapidly succumb to lymphocytic choriomeningitis virus (LCMV<\/jats:styled-content>) infection. Thus, vaccination converts a nonlethal persistent infection into a fatal disease mediated by virus\u2010specific memory CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content> cells. Here, we determine the extent to which vaccination\u2010induced mortality in PKO<\/jats:styled-content> mice following LCMV<\/jats:styled-content> challenge is due to differences in vaccine modalities, the quantity or epitope specificity of memory CD<\/jats:styled-content>8+<\/jats:sup> T<\/jats:styled-content> cells. We show that LCMV<\/jats:styled-content>\u2010induced mortality in immune PKO<\/jats:styled-content> mice is independent of vaccine modalities and that the starting number of memory CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content> cells specific to the immunodominant epitope NP<\/jats:styled-content>118\u2010126<\/jats:sub> dictates the magnitude of secondary CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content>\u2010cell expansion, the inability to regulate production of CD<\/jats:styled-content>8+<\/jats:sup> T<\/jats:styled-content>\u2010cell\u2010derived IFN<\/jats:styled-content>\u2010\u03b3, and mortality in the vaccinated PKO<\/jats:styled-content> mice. Importantly, mortality is determined by the epitope specificity of memory CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content> cells and the associated degree of functional exhaustion and cytokine dysregulation but not the absolute magnitude of CD<\/jats:styled-content>8+<\/jats:sup><\/jats:bold> T<\/jats:styled-content>\u2010cell expansion. These data suggest that deeper understanding of the parameters that influence the outcome of vaccine\u2010induced diseases would aid rational vaccine design to minimize adverse outcomes after infection.<\/jats:p>","DOI":"10.1002\/eji.201142263","type":"journal-article","created":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T11:28:19Z","timestamp":1339154899000},"page":"1488-1499","source":"Crossref","is-referenced-by-count":8,"title":["Epitope specificity of memory CD<\/scp>8+<\/sup>T<\/scp> cells dictates vaccination\u2010induced mortality in LCMV<\/scp>\u2010infected perforin\u2010deficient mice"],"prefix":"10.1002","volume":"42","author":[{"given":"Nhat\u2010Long L.","family":"Pham","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir P.","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology University of Iowa Iowa City IA USA"},{"name":"Department of Pathology University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Harty","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology University of Iowa Iowa City IA USA"},{"name":"Department of Pathology University of Iowa Iowa City IA USA"},{"name":"Department of Microbiology University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00384.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2251"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri778"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.11.5535-5545.2004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141548"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00333-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80197-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.10854"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7518614"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5495.1354"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1383"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1128\/JVI.73.3.2527-2536.1999","article-title":"A role for perforin in downregulating T\u2010cell responses during chronic viral infection","volume":"73","author":"Matloubian M.","year":"1999","journal-title":"J. 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