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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, JA; Lydyard, PM; Nathwani, A; Emery, V; Akbar, A; Glennie, MJ; Porakishvili, N; (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. BRIT J HAEMATOL , 148 (2) 274 - 284. 10.1111/j.1365-2141.2009.07964.x.

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Abstract

P>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.

Type: Article
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
DOI: 10.1111/j.1365-2141.2009.07964.x
Keywords: chronic lymphocytic leukaemia, cytomegalovirus, cytotoxicity, cytotoxic CD4 cells, HIGH-LEVEL REPLICATION, VIRUS-INFECTIONS, IN-VIVO, CD4(+), TRANSPLANTATION, RESPONSES, DISEASE, LOAD, HETEROGENEITY, PERSISTENCE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/89962
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