{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:36:01Z","timestamp":1791509761040,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T00:00:00Z","timestamp":1344211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"\n Chronic viral infections lead to\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n \u2010cell exhaustion, characterized by impaired cytokine secretion and loss of proliferative capacity. While viral load and\n T<\/jats:styled-content>\n \u2010cell dysfunction correlate, it is currently unclear whether the quality of a cell type presenting antigen determines the degree of\n T<\/jats:styled-content>\n \u2010cell exhaustion or if the overall amount of antigen recognized by\n T<\/jats:styled-content>\n cells promotes exhaustion. We found that chronic lymphocytic chorio\u2010meningitis virus infection led to decreased\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n \u2010cell exhaustion in\n DC<\/jats:styled-content>\n \u2010\n MHC<\/jats:styled-content>\n class I (\n MHCI<\/jats:styled-content>\n ) mice, in which\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n cells can only recognize antigen on\n DC<\/jats:styled-content>\n s. However, this increase in\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n \u2010cell function came at the expense of fatal immunopathology. Additional antigen recognition on nonhematopoietic cells in\n DC<\/jats:styled-content>\n \u2010\n MHCI<\/jats:styled-content>\n mice promoted\n T<\/jats:styled-content>\n \u2010cell exhaustion and avoidance of immunopathology. Likewise, increased numbers of antigen\u2010expressing hematopoietic cells, as well as a selective elevation of the number of\n DC<\/jats:styled-content>\n s as the only cell type presenting antigen in\n DC<\/jats:styled-content>\n \u2010\n MHCI<\/jats:styled-content>\n mice, resulted in compromised\n T<\/jats:styled-content>\n \u2010cell function. These results favor a scenario in which the overall amount of antigen exposure, rather than the type of cell engaging with virus\u2010specific\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n cells, is responsible for their functional exhaustion. Furthermore, exhaustion of virus\u2010specific\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T<\/jats:styled-content>\n cells leads to avoidance of life\u2010threatening immunopathology.\n <\/jats:p>","DOI":"10.1002\/eji.201142275","type":"journal-article","created":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T05:55:07Z","timestamp":1338530107000},"page":"2290-2304","source":"Crossref","is-referenced-by-count":55,"title":["Antigen amount dictates\n CD<\/scp>\n 8\n +<\/sup>\n T<\/scp>\n \u2010cell exhaustion during chronic viral infection irrespective of the type of antigen presenting cell"],"prefix":"10.1002","volume":"42","author":[{"given":"Kirsten","family":"Richter","sequence":"first","affiliation":[{"name":"Institute of Microbiology ETH Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Brocker","sequence":"additional","affiliation":[{"name":"Institute for Immunology Ludwig\u2010Maximilian\u2010University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Oxenius","sequence":"additional","affiliation":[{"name":"Institute of Microbiology ETH Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2009.02459.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.06.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5550-5558.2001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.18-4-230"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020656300027"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9848"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.7.2505"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1182\/blood.V96.9.3094","article-title":"Impaired function of circulating HIV\u2010specific CD8(+) T cells in chronic human immunodeficiency virus infection","volume":"96","author":"Shankar P.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610335104"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2205"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.7.4204"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/362758a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1492"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061462"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208421"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.06.015"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100213108"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"8056","DOI":"10.1128\/jvi.68.12.8056-8063.1994","article-title":"CD4+ \n T cells are required to sustain CD8 +cytotoxic T\u2010cell responses during chronic viral infection","volume":"68","author":"Matloubian M.","year":"1994","journal-title":"J. Virol."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174182"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172815"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175194"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02383-07"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809818106"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050100"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","unstructured":"Day C. L. Abrahams D. A. Lerumo L. Janse van Rensburg E. Stone L. O'Rie T. Pienaar B.et al. Functional capacity ofMycobacterium tuberculosis\u2010specific T cell responses in humans is associated with mycobacterial load.J. Immunol.2011.","DOI":"10.4049\/jimmunol.1101122"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.8.4799"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.7.3920"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.18.8781-8791.2001"},{"key":"e_1_2_7_33_1","first-page":"263","article-title":"Murine hepatitis caused by lymphocytic choriomeningitis virus. I. The hepatic lesions","volume":"70","author":"Lohler J.","year":"1994","journal-title":"Lab. Invest."},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702579104"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.5.763"},{"key":"e_1_2_7_36_1","first-page":"3239","article-title":"Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte\u2010macrophage colony\u2010stimulating factor or Flt3\u2010ligand","volume":"60","author":"Mach N.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.10.1555"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1996.0023"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2007.11.018"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215549804600404"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.69.2.1059-1070.1995"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.9.1249"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.12.7340-7349.1993"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011998107"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800997"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40040"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008437107"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1998.1344"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231237"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07591"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009731107"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.12.2043"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1439"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/346629a0"},{"key":"e_1_2_7_58_1","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.4049\/jimmunol.157.6.2618","article-title":"IL\u20106 is an in vitro and in vivo autocrine growth factor for middle T antigen\u2010transformed endothelial cells","volume":"157","author":"Giraudo E.","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.94"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201142275","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201142275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T08:56:51Z","timestamp":1695459411000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201142275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,6]]},"references-count":58,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1002\/eji.201142275"],"URL":"https:\/\/doi.org\/10.1002\/eji.201142275","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717976901.793470614","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,6]]}}}