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Strategy","award":["TTU-05-708"],"award-info":[{"award-number":["TTU-05-708"]}]},{"name":"(DFG, German Research Foundation) under Germany\u2019s Excellence Strategy","award":["158989968"],"award-info":[{"award-number":["158989968"]}]},{"name":"(DFG, German Research Foundation) under Germany\u2019s Excellence Strategy","award":["390874280"],"award-info":[{"award-number":["390874280"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Immunological memory to a previously encountered pathogen can influence the outcome of a sequential infection, which is called heterologous immunity. Lymphocytic choriomeningitis virus (LCMV) immune mice develop a NP205-specific T cell response that is cross-reactive to Pichinde virus infection (PICV). So far, limited data are available if cross-reactive T cell responses appear also during chronic infections with exhausted T cell responses. Exhaustion in chronic viral infections can be treated with checkpoint inhibitors, which might affect heterologous outcomes unexpectedly. The aim of this study was to investigate the cross-reactive immune response in chronic LCMV clone 13 (LCMVcl13) infection during primary PICV infection at phenotypic, functional, and T cell receptor (TCR) level. Moreover, the influence of checkpoint inhibitor therapy with \u03b1PD-L1 was investigated. Cross-reactive NP205-specific responses were present and functional in the chronic environment. Additionally, chronically infected mice were also protected from PICV mediated weight loss compared to naive PICV mice. An altered phenotype of NP205-specific T cells was detectable, but no major differences in the clonality and diversity of their TCR repertoire were observed. Checkpoint inhibitor treatment with \u03b1PD-L1 did alter chronic LCMV infection but had no major effect on heterologous immunity to PICV. Our study demonstrated that cross-reactive CD8+ T cells also exist in the setting of chronic infection, indicating a clinically relevant role of cross-reactive T cells in chronic infections.<\/jats:p>","DOI":"10.3390\/v14102293","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T02:54:25Z","timestamp":1666148065000},"page":"2293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cross-Reactive T Cell Response Exists in Chronic Lymphocytic Choriomeningitis Virus Infection upon Pichinde Virus Challenge"],"prefix":"10.3390","volume":"14","author":[{"given":"Jasmin","family":"Mischke","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany"},{"name":"Centre for Individualised Infection Medicine (CiiM), 30625 Hannover, Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany"},{"name":"Centre for Individualised Infection Medicine (CiiM), 30625 Hannover, Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-0428","authenticated-orcid":false,"given":"Austin","family":"Seamann","sequence":"additional","affiliation":[{"name":"School of Interdisciplinary Informatics, College of Information Science & Technology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immo","family":"Prinz","sequence":"additional","affiliation":[{"name":"Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany"},{"name":"Institute of Immunology, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liisa","family":"Selin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-0843","authenticated-orcid":false,"given":"Dario","family":"Ghersi","sequence":"additional","affiliation":[{"name":"School of Interdisciplinary Informatics, College of Information Science & Technology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Cornberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany"},{"name":"Centre for Individualised Infection Medicine (CiiM), 30625 Hannover, Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke R.M.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany"},{"name":"Centre for Individualised Infection Medicine (CiiM), 30625 Hannover, Germany"},{"name":"TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1172\/JCI27804","article-title":"Narrowed TCR Repertoire and Viral Escape as a Consequence of Heterologous Immunity","volume":"116","author":"Cornberg","year":"2006","journal-title":"J. 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