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

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@article{1950ff295c814cdabf68dc0ee5625764,
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",
abstract = "Advanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (T(regs)). 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+ CD25(low) population, whereas the number of CD4+ CD25(high) FoxP3+ cells was unchanged. CD4+ CD25(low) 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.",
author = "Karen Piper and M Karanth and Andrew McLarnon and E Kalk and Naeem Khan and James Murray and Guy Pratt and Paul Moss",
year = "2011",
month = nov,
day = "1",
doi = "10.1111/j.1365-2249.2011.04466.x",
language = "English",
volume = "166",
pages = "154--63",
journal = "Clinical & Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley",
number = "2",

}

RIS

TY - JOUR

T1 - 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

AU - Piper, Karen

AU - Karanth, M

AU - McLarnon, Andrew

AU - Kalk, E

AU - Khan, Naeem

AU - Murray, James

AU - Pratt, Guy

AU - Moss, Paul

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Advanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (T(regs)). 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+ CD25(low) population, whereas the number of CD4+ CD25(high) FoxP3+ cells was unchanged. CD4+ CD25(low) 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.

AB - Advanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (T(regs)). 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+ CD25(low) population, whereas the number of CD4+ CD25(high) FoxP3+ cells was unchanged. CD4+ CD25(low) 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.

U2 - 10.1111/j.1365-2249.2011.04466.x

DO - 10.1111/j.1365-2249.2011.04466.x

M3 - Article

C2 - 21985361

VL - 166

SP - 154

EP - 163

JO - Clinical & Experimental Immunology

JF - Clinical & Experimental Immunology

SN - 0009-9104

IS - 2

ER -