{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:03:45Z","timestamp":1791223425865,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,1,4]]},"abstract":"<jats:p>\n                    CTLA-4, an Ig superfamily molecule with homology to CD28, is one of the most potent negative regulators of T-cell responses. In vivo blockade of CTLA-4 exacerbates autoimmunity, enhances tumor-specific T-cell responses, and may inhibit the induction of T-cell anergy. Clinical trials of CTLA-4\u2013blocking antibodies to augment T-cell responses to malignant melanoma are at an advanced stage; however, little is known about the effects of CTLA-4 blockade on memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses and the formation and maintenance of long-term CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell memory. In our studies, we show that during in vivo memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses to\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    infection, CTLA-4 blockade enhances bacterial clearance and increases memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell expansion. This is followed by an accumulation of memory cells that are capable of producing the effector cytokines IFN-\u03b3 and TNF-\u03b1. We also demonstrate that in a vaccination setting, blocking CTLA-4 during CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell priming leads to increased expansion and maintenance of antigen-specific memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells without adversely affecting the overall T-cell repertoire. This leads to an increase in memory cell effector function and improved protective immunity against further bacterial challenges. These results indicate that transient blockade of CTLA-4 enhances memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses and support the possible use of CTLA-4\u2013blocking antibodies during vaccination to augment memory formation and maintenance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1016791108","type":"journal-article","created":{"date-parts":[[2010,12,20]],"date-time":"2010-12-20T23:23:52Z","timestamp":1292887432000},"page":"266-271","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":157,"title":["Single dose of anti\u2013CTLA-4 enhances CD8\n                    <sup>+<\/sup>\n                    T-cell memory formation, function, and maintenance"],"prefix":"10.1073","volume":"108","author":[{"given":"Virginia A.","family":"Pedicord","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Welby","family":"Montalvo","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Leiner","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Allison","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,12,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2533"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90071-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90125-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5238.985"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35105024"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.2.435"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0028"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.2.183"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3786-3792.1999"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1461"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.259"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.116.3.381"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/364798a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90163-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199810)28:10<3137::AID-IMMU3137>3.0.CO;2-X"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/44385"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082492"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_3_20_2","article-title":"A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naive patients with advanced melanoma","author":"Hersh EM","year":"2010","unstructured":"EM Hersh, et al., A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naive patients with advanced melanoma. Invest New Drugs, in press. (2010).","journal-title":"Invest New Drugs"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3181a7450f"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04790"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070543"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1122927"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4376"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.17.9296"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1016791108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:51:15Z","timestamp":1649793075000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1016791108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,20]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1,4]]}},"alternative-id":["10.1073\/pnas.1016791108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1016791108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,20]]},"assertion":[{"value":"2010-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}