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We determined the pattern of expression of forkhead box P3 (FoxP3), CD25, CD27 and CD127 and showed that the frequency of CD4+FoxP3+ T cells was increased in CLL patients (12% versus 8% in controls). This increase was seen only in advanced disease, with selective expansion of FoxP3-expressing cells in the CD4+CD25low population, whereas the number of CD4+CD25highFoxP3+ cells was unchanged. CD4+CD25low cells showed reduced expression of CD127 and increased CD27, and this regulatory phenotype was also seen on all CD4 T cells subsets in CLL patients, irrespective of CD25 or FoxP3 expression. Incubation of CD4+ T cells with primary CLL tumours led to a sixfold increase in the expression of FoxP3 in CD4+CD25- T cells. Patients undergoing treatment with fludarabine demonstrated a transient increase in the percentage of CD4+FoxP3+ T cells, but this reduced to normal levels post-treatment. This work demonstrates that patients with CLL exhibit a systemic T cell dysregulation leading to the accumulation of CD4+FoxP3+ T cells. This appears to be driven by interaction with malignant cells, and increased understanding of the mechanisms that are involved could provide novel avenues for treatment.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2011.04466.x","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T12:40:53Z","timestamp":1312461653000},"page":"154-163","source":"Crossref","is-referenced-by-count":45,"title":["Chronic lymphocytic leukaemia cells drive the global CD4+ T cell repertoire towards a regulatory phenotype and leads to the accumulation of CD4+ forkhead box P3+ T cells"],"prefix":"10.1093","volume":"166","author":[{"given":"K P","family":"Piper","sequence":"first","affiliation":[{"name":"School of Cancer Sciences, University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Karanth","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"McLarnon","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Kalk","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Immunology, School of Infection & Host Defence, University Of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Murray","sequence":"additional","affiliation":[{"name":"Centre for Clinical Haematology, Queen Elizabeth Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Pratt","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, University of 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