{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:38:49Z","timestamp":1791121129590,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,11,2]],"date-time":"2004-11-02T00:00:00Z","timestamp":1099353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SAF2003\u20100987\u2010CO2\u201001"],"award-info":[{"award-number":["SAF2003\u20100987\u2010CO2\u201001"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SAF2003\u20100987\u2010CO2\u201002"],"award-info":[{"award-number":["SAF2003\u20100987\u2010CO2\u201002"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>The participation of CD94 and NKG2 gene family members in the function of NK cells and CD8<jats:sup>+<\/jats:sup> cytolytic cells has recently been addressed in detail. However, the role that these molecules play in the key CD4<jats:sup>+<\/jats:sup> regulatory cells remains largely unexplored. This study has examined the expression and regulation of CD94 and NKG2 genes in purified human peripheral CD4<jats:sup>+<\/jats:sup> cells stimulated with several agents. We found a constitutive expression of NKG2\u2010E in CD94\u2010depleted resting peripheral CD4<jats:sup>+<\/jats:sup> cells, whereas inductions of NKG2\u2010A and NKG2\u2010C required chronic cell activation and occurred after expression of CD94. We found that CD3\u2010mediated stimulation induces the expression of CD94 first by day 5 of culture, followed by NKG2\u2010A by day 15 and finally NKG2\u2010C, which is not detected until 20 days after repeated stimulation. This pattern of gene expression differs sharply from that observed in purified CD8<jats:sup>+<\/jats:sup> T cells, where mRNA from all NKG2 gene family members are detected after 5 days of stimulation. Selective activation of TCR V\u03b2<jats:sub>2<\/jats:sub>\u2010bearing cells with toxic shock syndrome toxin\u20101 superantigen reveals that mRNA induction of NKG2\u2010A and NKG2\u2010C genes is significantly influenced by the presence of cytokines (IL\u201010 and TGF\u2010\u03b2) and by the restimulation of the cells. In addition, the occupancy of the CD94\/NKG2\u2010A receptor expressed on these superantigen\u2010stimulated CD4<jats:sup>+<\/jats:sup> T lymphocytes abrogates TNF\u2010\u03b1 and IFN\u2010 \u03b3 production, whereas NKG2\u2010C enhances production of these cytokines. Taken together our results reveal strict gene regulatory mechanisms for CD94 and NKG2 gene expression on CD4<jats:sup>+<\/jats:sup> cells that are different from those governing the expression of these same genes in CD8<jats:sup>+<\/jats:sup> cells. The results suggest that these genes also participate in chronic CD4<jats:sup>+<\/jats:sup> T\u2010cell responses.<\/jats:p>","DOI":"10.1111\/j.0818-9641.2004.01284.x","type":"journal-article","created":{"date-parts":[[2004,11,15]],"date-time":"2004-11-15T19:05:13Z","timestamp":1100545513000},"page":"587-595","source":"Crossref","is-referenced-by-count":8,"title":["Role for NKG2\u2010A and NKG2\u2010C surface receptors in chronic CD4<sup>+<\/sup> T\u2010cell responses"],"prefix":"10.1111","volume":"82","author":[{"given":"Consuelo","family":"Ortega","sequence":"first","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Romero","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Palma","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Orta","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Garc\u00eda\u2010Vinuesa","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio J","family":"Molina","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Universidad de Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda, Facultad de Medicina, Servicio de Inmunolog\u00eda Hospital Universitario \u2018Reina Sof\u00eda\u2019  Universidad de C\u00f3rdoba C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,11,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80048-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/83130"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100301.064812"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250904"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050276"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270230"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80441-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.8.3603"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.5.813"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00943.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271111"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.4049\/jimmunol.157.7.2804","article-title":"Clonotypic differences in signaling from CD94 (kp43) on NK cells lead to divergent cellular responses","volume":"157","author":"Brumbaugh KM","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<327::AID-IMMU327>3.0.CO;2-O"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.3.1172"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.4864"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<23::AID-IMMU23>3.0.CO;2-Y"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00833.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.2.219"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.4980"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00427-2"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)87461-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80394-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-3274(97)80038-X"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.6.923"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.3.981"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.1107"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.10.5382"}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.0818-9641.2004.01284.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.0818-9641.2004.01284.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/j.0818-9641.2004.01284.x","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.0818-9641.2004.01284.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:03:20Z","timestamp":1694066600000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.0818-9641.2004.01284.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11,2]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["10.1111\/j.0818-9641.2004.01284.x"],"URL":"https:\/\/doi.org\/10.1111\/j.0818-9641.2004.01284.x","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11,2]]}}}