{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:42:35Z","timestamp":1782150155731,"version":"3.54.5"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sustained Ag persistence in chronic infection results in a deregulated CD8+ T cell response that is characterized by T cell exhaustion and cell death of Ag-specific CD8+ T cells. Yet, the underlying transcriptional mechanisms regulating CD8+ T cell exhaustion and cell death are poorly defined. Using the experimental mouse model of lymphocytic choriomeningitis virus infection, we demonstrate that the transcriptional regulator Id3 controls cell death of virus-specific CD8+ T cells in chronic infection. By comparing acute and chronic infection, we showed that Id3\u2212 virus-specific CD8+ T cells were less abundant, whereas the absolute numbers of Id3+ virus-specific CD8+ T cells were equal in chronic and acute infection. Phenotypically, Id3\u2212 and Id3+ cells most prominently differed with regard to expression of the surface receptor 2B4; although Id3\u2212 cells were 2B4+, almost all Id3+ cells lacked expression of 2B4. Lineage-tracing experiments showed that cells initially expressing Id3 differentiated into Id3\u22122B4+ cells; in turn, these cells were terminally differentiated and highly susceptible to cell death under conditions of persisting Ag. Enforced Id3 expression specifically increased the persistence of 2B4+ virus-specific CD8+ T cells by decreasing susceptibility to Fas\/Fas ligand\u2013mediated cell death. Thus, our findings reveal that the transcriptional regulator Id3 promotes the survival of virus-specific CD8+ T cells in chronic infection and suggest that targeting Id3 might be beneficial for preventing cell death of CD8+ T cells in chronic infection or for promoting cell death of uncontrolled, hyperactive CD8+ T cells to prevent immunopathology.<\/jats:p>","DOI":"10.4049\/jimmunol.1402607","type":"journal-article","created":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T02:30:11Z","timestamp":1438396211000},"page":"2103-2114","source":"Crossref","is-referenced-by-count":17,"title":["Id3 Controls Cell Death of 2B4+ Virus-Specific CD8+ T Cells in Chronic Viral Infection"],"prefix":"10.1093","volume":"195","author":[{"given":"Alexandra J","family":"Menner","sequence":"first","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg , 79106 Freiburg ,","place":["Germany"]},{"name":"Faculty of Biology, University of Freiburg , 79106 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina S","family":"Rauch","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg , 79106 Freiburg ,","place":["Germany"]},{"name":"Faculty of Biology, University of Freiburg , 79106 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Aichele","sequence":"additional","affiliation":[{"name":"Center for Microbiology and Hygiene, Institute for Immunology, University Medical Center and University of Freiburg , 79104 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter","family":"Pircher","sequence":"additional","affiliation":[{"name":"Center for Microbiology and Hygiene, Institute for Immunology, University Medical Center and University of Freiburg , 79104 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schachtrup","sequence":"additional","affiliation":[{"name":"Department of Molecular Embryology, Institute of Anatomy and Cell Biology, University of Freiburg , 79104 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Schachtrup","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg , 79106 Freiburg ,","place":["Germany"]},{"name":"Faculty of Biology, University of Freiburg , 79106 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704072049600_r1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech","year":"2012","journal-title":"Nat. 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