| Title | Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4(+) perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype |
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| Authors | Walton, J.A., Lydyard, P.M., Nathwani, A., Emery, V., Akbar, A., Glennie, M.J. and Porakishvili, N. |
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| Abstract | Summary - We have previously shown an expansion of cytotoxic antigen-experienced CD4(+)T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL). Increased frequencies of CD4(+)CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4(+)CTLs in responses to HCMV in B-CLL, and characterized their differentiation. We studied 36 HCMV seropositive (SP) and seronegative B-CLL patients and 20 healthy age-matched individuals. The HCMV reactivity of CD4(+)PF(+) and CD4(+)PF(-) cells was determined by interferon-gamma expression, and expression of CD45RA and CCR7 was assessed by flow cytometry. Fluorescence in-situ hybridization was used to measure relative telomere lengths. CD4(+)PF(+)T cell expansion in B-CLL patients and controls was strongly associated with HCMV seropositivity. CD4(+)PF(+) compared to CD4(+)PF(-) cells from SP B-CLL patients elicited major histocompatibility complex (MHC) class II-restricted responses to HCMV. CD4(+)PF(+)T cells from patients and controls were enriched with highly differentiated T-effector/memory (CCR7(-)) and revertant (CCR7(-)CD45RA(+)) phenotype. CD4(+)PF(+)T cells from B-CLL patients had shorter telomeres than CD4(+)PF(-)T cells, indicating an extensive replicative history. We conclude that persistent exposure to HCMV antigens in SP B-CLL patients leads to an expansion of the circulating MHC class II-restricted CD4(+)PF(+)T cell population with effector/memory phenotype. |
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| Journal | British Journal of Haematology |
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| Journal citation | 148 (2), pp. 274-284 |
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| ISSN | 0007-1048 |
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| Year | 29 Jan 2010 |
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| Publisher | Wiley |
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| Digital Object Identifier (DOI) | https://doi.org/10.1111/j.1365-2141.2009.07964.x |
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| Publication dates |
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| Published | 29 Jan 2010 |
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