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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

Walton, James A. and Lydyard, Peter M. and Nathwani, Amit and Emery, Vincent and Akbar, Arne and Glennie, Martin J. and Porakishvili, Nino (2010) 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. British Journal of Haematology, 148 (2). pp. 274-284. ISSN 0007-1048

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Official URL: http://dx.doi.org/10.1111/j.1365-2141.2009.07964.x

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.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:7042
Deposited On:25 Nov 2009 14:40
Last Modified:11 Mar 2010 15:19

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