{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:24:57Z","timestamp":1791321897826,"version":"4.3.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1998,6,1]],"date-time":"1998-06-01T00:00:00Z","timestamp":896659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,25]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>S\u00e9zary syndrome (SzS) is the leukaemic variant of cutaneous T cell lymphoma (CTCL), whose malignant T cells are of the Th2 type in most cases. In this study we investigated the tumouricidal activity of cytotoxic T lymphocytes (CTL) present in peripheral blood of a patient with Th2-type SzS, focusing on the effect of IL-2, IFN-\u03b3 and IL-12 on their cytotoxic activity, and the relationship between their lytic capacity and the patient's clinical course. At four different time points during a 2-month clinical period, CD4+ CD7\u2212 S\u00e9zary cells and CD8+ cells were separated from the patient's circulating cells. CD8+ cells were cultured with chemically attenuated, purified S\u00e9zary cells in the presence of IL-2 to develop specific cytotoxicity. The CD8+ cells thus cultured exhibited lytic activity against autologous S\u00e9zary cells. Concomitant addition of IFN-\u03b3 or IL-12 exerted a synergistic cytolytic effect with IL-2 on the tumour cells. Cytotoxicity inhibition studies using MoAbs revealed that the cytotoxicity operated in MHC class I-, CD8- and \u03b1\u03b2 T cell receptor-dependent manners. Furthermore, eight CD8+ T cell clones generated from cultured CD8+ cells exhibited a strong cytotoxicity against S\u00e9zary cells in an MHC class I-restricted fashion. During the clinical course, the activity of generated CTL and the number of CD8+ cells were inversely correlated with disease activity as assessed by the serum level of lactate dehydrogenase. These findings suggest that CTL down-regulate the growth of malignant T cells in this long-standing disease. Since Th2 cytokines such as IL-4 down-modulate CTL activity, CTL are assumed to be usually suppressed in SzS, whose malignant T cells are of Th2 type. It is likely that the administration of IFN-\u03b3 normalizes this Th2-skewing state, activates CTL, and thus exerts the therapeutic effectiveness in the treatment of CTCL.<\/jats:p>","DOI":"10.1046\/j.1365-2249.1998.00599.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:11:12Z","timestamp":1047377472000},"page":"403-409","source":"Crossref","is-referenced-by-count":36,"title":["Tumour-specific cytotoxic T lymphocyte activity in Th2-type S\u00e9zary syndrome: its enhancement by interferon-gamma (IFN-\u03b3) and IL-12 and fluctuations in association with disease activity"],"prefix":"10.1093","volume":"112","author":[{"given":"N","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Tokura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Takigawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,12,25]]},"reference":[{"key":"b1_213","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0065-2776(08)60664-1","volume":"47","author":"Trinchieri G","year":"1989","journal-title":"Adv Immunol"},{"key":"b2_214","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.12.1.337"},{"key":"b3_215","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0167-5699(91)90018-O","volume":"12","author":"Rotzschke O","year":"1991","journal-title":"Immunol Today"},{"key":"b4_216","doi-asserted-by":"publisher","DOI":"10.1038\/384109a0"},{"key":"b5_217","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1126\/science.7863326","volume":"267","author":"Malnati MS","year":"1995","journal-title":"Science"},{"key":"b6_218","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nm0196-52","volume":"2","author":"Hsu FJ","year":"1996","journal-title":"Nature Med"},{"key":"b7_219","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1084\/jem.183.1.7","volume":"183","author":"Young JW","year":"1996","journal-title":"J Exp Med"},{"key":"b8_220","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.7.1.145"},{"key":"b9_221","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJM198812223192527","volume":"319","author":"Rosenberg SA","year":"1988","journal-title":"N Engl J Med"},{"key":"b10_222","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/0008-8749(88)90109-8","volume":"111","author":"Siegel JP","year":"1988","journal-title":"Cell Immunol"},{"key":"b11_223","doi-asserted-by":"publisher","DOI":"10.1007\/s002620050065"},{"key":"b12_224","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0190-9622(80)80385-9","volume":"2","author":"Edelson R","year":"1980","journal-title":"J Am Acad Dermatol"},{"key":"b13_225","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/jnci\/83.6.400","volume":"83","author":"Heald P","year":"1991","journal-title":"J Natl Cancer Inst"},{"key":"b14_226","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/1523-1747.ep12611877","volume":"99","author":"Vowels BR","year":"1992","journal-title":"J Invest Dermatol"},{"key":"b15_227","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/1523-1747.ep12388985","volume":"103","author":"Saed G","year":"1994","journal-title":"J Invest Dermatol"},{"key":"b16_228","first-page":"4430","volume":"54","author":"Tendler CL","year":"1994","journal-title":"Cancer Res"},{"key":"b17_229","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0190-9622(07)80011-9","volume":"34","author":"Yagi H","year":"1996","journal-title":"J Am Acad Dermatol"},{"key":"b18_230","unstructured":"18 PW Heald, and RL Edelson . 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