{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:48:20Z","timestamp":1790056100043,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TP1"],"award-info":[{"award-number":["TP1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["2"],"award-info":[{"award-number":["2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["3"],"award-info":[{"award-number":["3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["14"],"award-info":[{"award-number":["14"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["15"],"award-info":[{"award-number":["15"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["17"],"award-info":[{"award-number":["17"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Z1"],"award-info":[{"award-number":["Z1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial hemophagocytic lymphohistiocytosis (FHL) is a hyperinflammatory syndrome affecting patients with genetic cytotoxicity defects. Perforin\u2010deficient (PKO) mice recapitulate the full clinical picture of FHL after infection with lymphocytic choriomeningitis virus (LCMV). Hyperactivated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells and IFN\u2010\u03b3 have been identified as the key drivers of FHL and represent targets for therapeutic interventions. However, the response of patients is variable. This could be due to trigger\u2010dependent differences in pathogenesis, which is difficult to address in FHL patients, since the trigger frequently escapes detection. We established an alternative FHL model using intravenous infection of PKO mice with murine CMV (MCMV)\n                    <jats:sub>Smith<\/jats:sub>\n                    . PKO mice developed acute FHL after both infections and fulfilled HLH diagnostic criteria accompanied by excessive IFN\u2010\u03b3 production by disease\u2010inducing T\u00a0cells, that enrich in the BM. However, direct comparison of the two infection models disclosed trigger\u2010dependence of FHL progression and revealed a higher contribution of CD4 T\u00a0cells and NK cells to IFN\u2010\u03b3 production after MCMV infection. Importantly, therapeutic intervention by IFN\u2010\u03b3 neutralization or CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell depletion had less benefit in MCMV\u2010triggered FHL compared to LCMV\u2010triggered FHL, likely due to MCMV\u2010induced cytopathology. Thus, the context of the specific triggering viral infection can impact the success of targeted immunotherapeutic HLH control.\n                  <\/jats:p>","DOI":"10.1002\/eji.201948123","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T02:20:10Z","timestamp":1589768410000},"page":"1770-1782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Trigger\u2010dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis"],"prefix":"10.1002","volume":"50","author":[{"given":"Ruth","family":"Gather","sequence":"first","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Institute for Immunodeficiency Medical Center University of Freiburg  Germany"},{"name":"Faculty of Biology University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Aichele","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Immunology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Goos","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Institute for Immunodeficiency Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rohr","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Institute for Immunodeficiency Medical Center University of Freiburg  Germany"},{"name":"Center for Pediatrics and Adolescent Medicine Faculty of Medicine Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-9589","authenticated-orcid":false,"given":"Hanspeter","family":"Pircher","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Immunology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"K\u00f6gl","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Immunology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Hengel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Virology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Schmitt\u2010Gr\u00e4ff","sequence":"additional","affiliation":[{"name":"Department of General Pathology Faculty of Medicine Institute of Pathology Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medicine University of Alabama  Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-2721","authenticated-orcid":false,"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Institute for Immunodeficiency Medical Center University of Freiburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-041610-134208"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.08.004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5446.1957"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40732"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00855-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi076"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1993.tb12699.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/323675"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3413"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.11.1903"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00448"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-441139"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-495309"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.11.4100"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-3164"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911326"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27344"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80033-1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80469-0"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.275"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.10.001"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501035"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-017-0908-0"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.4.1045"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.4049\/jimmunol.131.3.1531","article-title":"Natural killer cell depletion enhances virus synthesis and virus\u2010induced hepatitis in vivo","volume":"131","author":"Bukowski J. F.","year":"1983","journal-title":"J. Immunol."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.09.010"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00239"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-015-0409-y"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06672"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356113"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000841"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.3.1895-1902.1995"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.1.661-667.2005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.1.267-275.1997"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.41"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.4049\/jimmunol.134.1.608","article-title":"Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice","volume":"134","author":"Lehmann\u2010Grube F.","year":"1985","journal-title":"J. Immunol."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.6.1047"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.7815-7821.1998"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01246575"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.63.3.303"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.38.3.1046-1055.1982"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.3.577"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.69.3.1762-1768.1995"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-095414"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.3.2111"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007050070010"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788349"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"},{"key":"e_1_2_8_55_1","first-page":"Unit 19 17","article-title":"A mouse model for cytomegalovirus infection","volume":"19","author":"Brune W.","year":"2001","journal-title":"Curr. Protoc. Immunol."},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201948123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201948123","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T03:47:10Z","timestamp":1693799230000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201948123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,2]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/eji.201948123"],"URL":"https:\/\/doi.org\/10.1002\/eji.201948123","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201948123\/v3\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v4\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v4\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948123\/v3\/response1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,2]]},"assertion":[{"value":"2019-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}