{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:48:17Z","timestamp":1780638497939,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["256073931"],"award-info":[{"award-number":["256073931"]}],"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":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent findings indicate that many immunopathologies are at their roots a consequence of impaired immune responses (\u201ctoo little\u201d immunity) and not the result of primarily exaggerated immune responses (\u201ctoo much\u201d immunity). We have summarized this conceptional view as \u201c\n                    <jats:italic>IMPATH paradox<\/jats:italic>\n                    .\u201d In this review, we will focus on impaired immune reactions in the context of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell\u2010mediated immunopathologies. In particular, we will exemplify this concept in two disease models: Virus\u2010triggered primary hemophagocytic lymphohistiocytosis, an inflammatory syndrome caused by genetically impaired cytolytic functions of T cells, and viral hepatitis, where T\u2010cell exhaustion is a major underlying mechanism for impaired effector functions. In both situations, T cells fail to eliminate the source of immune stimulation, which usually serves as an important negative feedback loop curtailing immune reactions. Persistent antigen presentation by APCs and\/or infected cells results in continuous stimulation causing chronic inflammation and immunopathology mediated by residual T\u2010cell functions. Hence, immune stimulation or reconstitution rather than immune suppression may be strategies for therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149528","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T09:25:52Z","timestamp":1643621152000},"page":"1390-1395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunopathology caused by impaired CD8\n                    <sup>+<\/sup>\n                    T\u2010cell responses"],"prefix":"10.1002","volume":"52","author":[{"given":"Peter","family":"Aichele","sequence":"first","affiliation":[{"name":"Institute for Immunodeficiency Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Neumann\u2010Haefelin","sequence":"additional","affiliation":[{"name":"Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-2721","authenticated-orcid":false,"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[{"name":"Institute for Immunodeficiency Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Thimme","sequence":"additional","affiliation":[{"name":"Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Cathomen","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"Institute for Transfusion Medicine and Gene Therapy Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Freiburg, and German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8410-8833","authenticated-orcid":false,"given":"Maike","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases) Faculty of Medicine Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.04.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7518614"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00904.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/238335a0"},{"key":"e_1_2_9_7_1","first-page":"89","article-title":"T\u2010cell\u2010mediated immunopathology in viral infections","volume":"19","author":"Doherty P. 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