{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:39:20Z","timestamp":1790375960177,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2007,8,23]],"date-time":"2007-08-23T00:00:00Z","timestamp":1187827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (ATL) is a CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T\u2010cell malignancy infected with human T\u2010cell leukemia virus type\u2010I (HTLV\u2010I). HTLV\u2010I infection causes the T\u2010cell dysfunction, which contributes to the immunodeficient state of the patients. Programmed death\u20101 (PD\u20101) can negatively regulate T\u2010cell response, when its ligand, PD\u2010L1 or PD\u2010L2 mainly expressed on antigen presenting cells, binds to this B7 family receptor. We investigated whether PD\u20101 is expressed on CD4<jats:sup>+<\/jats:sup> neoplastic (and\/or non\u2010neoplastic) cells or CD8<jats:sup>+<\/jats:sup> cytotoxic cells in peripheral blood mononuclear cells from 11 patients with ATL. By flow cytometry, we found that the levels of PD\u20101 expression on both CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup> T\u2010cell populations were increased in ATL patients compared to normal healthy volunteers, while PD\u20101 levels on CD8<jats:sup>+<\/jats:sup> T\u2010cells were comparable between the patients and normal subjects. In stimulation with anti\u2010CD3 antibody, the proliferation of PD\u20101\u2010expressing T\u2010cells from ATL patients was weak when compared to that of PD\u20101\u2010nonexpressing normal T\u2010cells. In addition to PD\u20101, PD\u2010L1 was coexpressed on ATL cells in some patients, and PD\u2010L1 expression was enhanced by stimulation with anti\u2010CD3 antibody. Finally, the production of cytokines such as TNF\u2010\u03b1 by ATL cells was restored by blockade of PD\u20101\/PD\u2010L1 interaction. These findings suggest that CD4<jats:sup>+<\/jats:sup> T\u2010cells are the main PD\u20101\u2010expressing cells rather than CD8<jats:sup>+<\/jats:sup> T\u2010cells in ATL patients, and both neoplastic and normal CD4<jats:sup>+<\/jats:sup> cells are exhausted as a result of PD\u20101 expression, and additionally PD\u2010L1 expression on the neoplastic cell. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23042","type":"journal-article","created":{"date-parts":[[2007,8,25]],"date-time":"2007-08-25T00:22:54Z","timestamp":1188001374000},"page":"2585-2590","source":"Crossref","is-referenced-by-count":83,"title":["Augmented expression of programmed death\u20101 in both neoplastic and non\u2010neoplastic CD4<sup>+<\/sup> T\u2010cells in adult T\u2010cell 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