{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:44:49Z","timestamp":1781613889494,"version":"3.54.5"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,3,1]]},"abstract":"<jats:p>C.B-17 scid\/scid (severe combined immunodeficiency [SCID]) mice inoculated with peripheral blood lymphocytes from Epstein-Barr virus (EBV)-seropositive donors, or with EBV-transformed lymphoblastoid B cell lines (EBV-LCL), develop lethal human EBV+ B cell lymphoproliferative disorders (EBV-LPD) with characteristics similar to those arising in immunodeficient patients. Using this model, we examined the capacity of human effector cells to control human EBV-LPD. SCID mice received rabbit anti-asialo GM1 antiserum to abrogate endogenous natural killer-cell function. Preliminary experiments showed that adoptive transfer of peripheral blood mononuclear cells (PBMC), purified T cells, interleukin (IL) 2-activated PBMC or anti-CD3-activated T cells derived from EBV-seropositive donors did not result in improved survival of treated mice (in vivo effector\/target ratio 2:1 to 1:1). In contrast, EBV-specific cytotoxic T lymphocytes (CTL), derived from EBV-seropositive donors and expanded in vitro, exhibited strong EBV-specific and HLA-restricted activity both in vitro and in vivo. SCID mice inoculated intraperitoneally with autologous but not with HLA-mismatched EBV-LCL had significantly improved survival relative to untreated mice after inoculation of EBV-specific CTL either intraperitoneally (P&amp;lt;0.001) or intravenously (P&amp;lt;0.001) (in vivo effector\/target ratio 1:1). SCID mice bearing large subcutaneous EBV+ tumors and treated intravenously with 10(7) EBV-specific CTL achieved complete tumor regression. Both CTL- and CTL-plus-IL-2-treated mice survived significantly longer than untreated animals or animals treated with IL-2 alone (P = 0.0004 and P&amp;lt;0.02, respectively). SCID mice bearing two subcutaneous EBV+ tumors, one autologous and the other HLA mismatched to the EBV-specific CTL donor, had regression of only the autologous tumor after intravenous infusion of 10(7) EBV-specific CTL. Moreover, we could demonstrate preferential homing of PKH26-labeled EBV-specific CTL to autologous but not to HLA-mismatched EBV+ tumors as early as 24 h after intravenous adoptive transfer. Immunophenotypic analyses also demonstrated preferential infiltration of T cells into the autologous EBV+ tumor in SCID mice bearing both the autologous and either fully HLA-mismatched or genotypically related haplotype-sharing EBV+ tumors. The human T cells infiltrating EBV+ tumors were CD3+ and, predominantly, CD8+CD4-. Our results indicate that EBV-specific CTL preferentially localize to and infiltrate EBV+ tumors bearing the appropriate HLA antigens and thereafter induce targeted regressions of disease.<\/jats:p>","DOI":"10.1084\/jem.183.3.1215","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1215-1228","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV-induced B cell lymphoproliferations in xenografted C.B-17 scid\/scid mice."],"prefix":"10.1084","volume":"183","author":[{"given":"J F","family":"Lacerda","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ladanyi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D C","family":"Louie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E B","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1996,3,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/1215\/1678145\/1215.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/1215\/1678145\/1215.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:06:19Z","timestamp":1690268779000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/183\/3\/1215\/47876\/Human-Epstein-Barr-virus-EBV-specific-cytotoxic-T"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1996,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.183.3.1215","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,3,1]]}}}