{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:14:15Z","timestamp":1767064455959,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["CR5113_147662"],"award-info":[{"award-number":["CR5113_147662"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Epidemiological data suggest that persistent viral infections impair immune homeostasis and immune responsiveness. Previous studies showed that chronic virus infections negatively impact bystander T\u2010cell differentiation and memory formation but there is limited knowledge of how chronic virus infections impinge on heterologous naive T\u2010cell populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used adoptive transfer of naive CD8 T cells with defined nonviral specificity into hosts, which were subsequently chronically infected with lymphocytic choriomeningitis virus, followed by analyses of numeric, phenotypic, and functional changes provoked in the chronically infected host.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that chronic virus infections have a profound effect on the number and phenotype of naive bystander CD8 T cells. Moreover, primary expansion upon antigen encounter was severely compromised in chronically infected hosts. However, when naive bystander CD8 T cells were transferred from the chronically infected mice into naive hosts, they regained their expansion potential. Conversely, when chronically infected hosts were supplied with additional antigen\u2010presenting cells (APCs), primary expansion of the naive CD8 T cells was restored to levels of the uninfected hosts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results document numeric, phenotypic, and functional adaptation of bystander naive CD8 T cells during nonrelated chronic viral infection. Their functional impairment was only evident in the chronically infected host, indicating that T\u2010cell extrinsic factors, in particular the quality of priming APCs, are responsible for the impaired function of naive bystander T cells in the chronically infected hosts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.300","type":"journal-article","created":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T05:54:36Z","timestamp":1585288476000},"page":"249-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic viral infections impinge on naive bystander CD8 T cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Isabel","family":"Barnstorf","sequence":"first","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne P. M.","family":"Welten","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Borsa","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas S.","family":"Baumann","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Pallmer","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Joller","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Sp\u00f6rri","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-2354","authenticated-orcid":false,"given":"Annette","family":"Oxenius","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Department of Biology ETH Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,26]]},"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":"10.1038\/ni969"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.10.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3139"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181589"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.04.010"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302027"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","unstructured":"AlanioC NicoliF SultanikP et al.Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV 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