{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:45:43Z","timestamp":1759401943442},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2003,6,13]],"date-time":"2003-06-13T00:00:00Z","timestamp":1055462400000},"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":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>DNA vaccination is an efficient way to induce CD8<jats:sup>+<\/jats:sup> T\u2004cell memory, but it is still unclear to what extent such memory responses afford protection <jats:italic>in vivo<\/jats:italic>. To study this, we induced CD8<jats:sup>+<\/jats:sup> memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class\u2004I\u2010restricted epitopes of lymphocytic choriomeningitis virus covalently linked to \u03b22\u2010microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine\u2010primed CD8<jats:sup>+<\/jats:sup> T\u2004cells in uninfected mice differed from virus\u2010primed CD8<jats:sup>+<\/jats:sup> T\u2004cells particularly regarding expression of very\u2010late antigen (VLA)\u20104, an adhesion molecule important for targeting T\u2004cells to inflammatory sites. Thus, our DNA vaccine induces a long\u2010lived memory CD8<jats:sup>+<\/jats:sup> T\u2004cell population that provides efficient protection against high\u2010dose systemic infection. However, viral replication in solid non\u2010lymphoid organs is not curtailed sufficiently fast to prevent significant virus\u2010induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8<jats:sup>+<\/jats:sup> T\u2004cells.<\/jats:p>","DOI":"10.1002\/eji.200323928","type":"journal-article","created":{"date-parts":[[2003,6,20]],"date-time":"2003-06-20T11:13:35Z","timestamp":1056107615000},"page":"1941-1948","source":"Crossref","is-referenced-by-count":14,"title":["Incomplete effector\/memory differentiation of antigen\u2010primed CD8<sup>+<\/sup> T\u2004cells in gene gun DNA\u2010vaccinated mice"],"prefix":"10.1002","volume":"33","author":[{"given":"Christina","family":"Bartholdy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Stryhn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils\u2004Jakob\u2004Vest","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Buus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan\u2004Randrup","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,6,13]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80053-3"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1996.tb00694.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.54"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1996.tb00696.x"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.4.467"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80042-2"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/356152a0"},{"key":"e_1_2_7_8_2","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.4049\/jimmunol.160.5.2388","article-title":"Contribution of cells at the site of DNA vaccination to the generation of antigen\u2010specific immunity and memory.","volume":"160","author":"Klinman D. M.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.6.1075"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(96)00041-5"},{"key":"e_1_2_7_11_2","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.4049\/jimmunol.156.7.2369","article-title":"Induction of cytotoxic T\u2004lymphocytes and antitumor immunity with DNA vaccines expressing single T\u2004cell epitopes.","volume":"156","author":"Ciernik I. F.","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_7_12_2","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1128\/JVI.72.6.5174-5181.1998","article-title":"DNA immunization with minigenes: low frequency of memory cytotoxic T\u2004lymphocytes and inefficient antiviral protection are rectified by ubiquitination.","volume":"72","author":"Rodriguez F.","year":"1998","journal-title":"J. Virol."},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00950.x"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00279-0"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1998.00323.x"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf037"},{"key":"e_1_2_7_17_2","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1128\/jvi.66.4.2527-2531.1992","article-title":"Diversity of T\u2004cell receptors in virus\u2010specific cytotoxic T\u2004lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule.","volume":"66","author":"Yanagi Y.","year":"1992","journal-title":"J. Virol."},{"key":"e_1_2_7_18_2","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1128\/jvi.61.6.1867-1874.1987","article-title":"Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus\u2010infected mice with monoclonal antibodies reveals that Lyt\u20102+ T\u2004lymphocytes mediate clearance of virus and regulate the antiviral antibody response.","volume":"61","author":"Moskophidis D.","year":"1987","journal-title":"J. Virol."},{"key":"e_1_2_7_19_2","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1128\/jvi.62.6.2102-2106.1988","article-title":"T4+ T\u2004helper cell function in vivo: differential requirement for induction of antiviral cytotoxic T\u2004cell and antibody responses.","volume":"62","author":"Ahmed R.","year":"1988","journal-title":"J. Virol."},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1994.tb03477.x"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.4049\/jimmunol.157.7.3074","article-title":"Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus\u2010infected MHC class\u2004II\u2010deficient mice and B\u2004cell\u2010deficient mice.","volume":"157","author":"Thomsen A. R.","year":"1996","journal-title":"J. Immunol."},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-71987-5_7"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/123.2.134"},{"key":"e_1_2_7_24_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0167-5699(90)90019-6","article-title":"Dissectionof an inflammatory process induced by CD8+ T\u2004cells.","volume":"11","author":"Doherty P. C.","year":"1990","journal-title":"Immunol. Today"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830190302"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01754-0"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830160807"},{"key":"e_1_2_7_28_2","first-page":"357","article-title":"Virus\u2010induced cell\u2010mediated immunopathological disease. In Notkins, A. L. (Ed.) Viral immunology andimmunopathology.","author":"Nathanson N.","year":"1975","journal-title":"Academic Press, New York"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3689"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.6.859"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0637"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.12.6983"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.2.223"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.640"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9716"},{"key":"e_1_2_7_37_2","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.4049\/jimmunol.163.10.5535","article-title":"Naive, effector, and memory CD8 T\u2004cells in protection against pulmonary influenza virus infection: homing properties rather than initial frequencies are crucial.","volume":"163","author":"Cerwenka A.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_7_38_2","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.4049\/jimmunol.154.10.5293","article-title":"Alpha\u20044 integrin directs virus\u2010activated CD8+ T\u2004cells to sites of infection.","volume":"154","author":"Christensen J. P.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_2_7_40_2","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1128\/JVI.73.5.4279-4283.1999","article-title":"Quantitative analysis of the acute and long\u2010term CD4(+) T\u2004cell response to a persistent gammaherpesvirus.","volume":"73","author":"Christensen J. P.","year":"1999","journal-title":"J. Virol."},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.9.1453"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.200323928","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.200323928","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T23:00:34Z","timestamp":1700262034000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.200323928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,13]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2003,7]]}},"alternative-id":["10.1002\/eji.200323928"],"URL":"https:\/\/doi.org\/10.1002\/eji.200323928","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,13]]}}}