{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:25:44Z","timestamp":1793413544871,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009828","name":"Cancer Research Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009828","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Chronic lymphocytic leukaemia (CLL) patients often have abnormal expansions of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and this can be associated with progressive disease. To characterise the key T\u2010cell populations involved in this phenomenon, we used flow cytometry and 11 phenotypic markers to study 74 CLL patients and 14 controls. T cells of CLL patients were more phenotypically complex than those of healthy controls with significant increases in the frequencies of CD4 and CD8 memory T cells expressing exhaustion\u2010, activation\u2010 and senescence\u2010associated markers. Multivariate analysis of 111 different T\u2010cell subsets showed that high frequencies of four subsets (three CD8 and one CD4) were associated with shorter progression\u2010free survival. The most significant association was with CD4\n                    <jats:sup>+<\/jats:sup>\n                    HLA\u2010DR\n                    <jats:sup>+<\/jats:sup>\n                    PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and patients could be stratified into high\u2010 and low\u2010risk groups based on the frequency of these T cells. The expansion of this CD4\n                    <jats:sup>+<\/jats:sup>\n                    subset could not be accounted for by age, cytomegalovirus infection or increases in Treg cells. Overall, these results highlight two relatively simple biomarkers, percentage CD8\n                    <jats:sup>+<\/jats:sup>\n                    and percentage CD4\n                    <jats:sup>+<\/jats:sup>\n                    PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    HLA\u2010DR\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which can be used to risk\u2010stratify CLL patients, independent of other tumour\u2010associated markers. They also provide further evidence for the pivotal role of T cells in modulating the pathology of CLL.\n                  <\/jats:p>","DOI":"10.1111\/bjh.16260","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T08:27:57Z","timestamp":1573201677000},"page":"872-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Increased frequency of CD4\n                    <sup>+<\/sup>\n                    PD\u20101\n                    <sup>+<\/sup>\n                    HLA\u2010DR\n                    <sup>+<\/sup>\n                    T cells is associated with disease progression in CLL"],"prefix":"10.1111","volume":"188","author":[{"given":"Lauren","family":"Elston","sequence":"first","affiliation":[{"name":"Division of Cancer and Genetics Cardiff University School of Medicine Cardiff 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