{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:22:18Z","timestamp":1790392938478,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T00:00:00Z","timestamp":1492387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004160","name":"Mazandaran University of Medical Sciences","doi-asserted-by":"publisher","award":["MCBRC\u2010MAZUMS\u20101282"],"award-info":[{"award-number":["MCBRC\u2010MAZUMS\u20101282"]}],"id":[{"id":"10.13039\/501100004160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Abstract<\/jats:title>Objectives<\/jats:title>The phenotypic and functional properties of Tim\u20103+<\/jats:sup>\/PD<\/jats:styled-content>\u20101+<\/jats:sup>\/CD<\/jats:styled-content>8+<\/jats:sup> cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Frequency of CD<\/jats:styled-content>8+<\/jats:sup>\/Tim\u20103+<\/jats:sup>\/PD<\/jats:styled-content>\u20101+<\/jats:sup> exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads\u2010isolated CD<\/jats:styled-content>8+<\/jats:sup> T cells were stimulated with PHA<\/jats:styled-content> and PMA<\/jats:styled-content>\/ionocymin to assess their proliferative responses and cytokine production by MTT<\/jats:styled-content> and ELISA<\/jats:styled-content>, respectively. Cytotoxic activity of isolated CD<\/jats:styled-content>8+<\/jats:sup> T cells was determined using CD<\/jats:styled-content>107a degranulation assay.<\/jats:p><\/jats:sec>Results<\/jats:title>The proportion of exhausted CD<\/jats:styled-content>8+<\/jats:sup> T cells was significantly higher in CLL<\/jats:styled-content> compared to controls. Isolated CD<\/jats:styled-content>8+<\/jats:sup> T cells from CLL<\/jats:styled-content> showed functional defects in proliferation, degranulation, and cytokines production. While IL<\/jats:styled-content>\u20102, TNF<\/jats:styled-content>\u2010\u03b1, and IFN<\/jats:styled-content>\u2010\u03b3 were significantly lower in CLL<\/jats:styled-content> patients, IL<\/jats:styled-content>\u201010 was higher in the patients group. Patients with progressive clinical stages showed higher frequency and dysfunction of exhausted CD<\/jats:styled-content>8+<\/jats:sup> T cells.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12880","type":"journal-article","created":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T15:31:31Z","timestamp":1489764691000},"page":"622-631","source":"Crossref","is-referenced-by-count":47,"title":["Frequency and functional characterization of exhausted CD<\/scp>8+<\/sup> T cells in chronic lymphocytic leukemia"],"prefix":"10.1111","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-6046","authenticated-orcid":false,"given":"Saeid","family":"Taghiloo","sequence":"first","affiliation":[{"name":"Department of Immunology School of Medicine Mazandaran University of Medical Sciences 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