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
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
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.
chronic lymphocytic leukaemia, cytomegalovirus, cytotoxicity, cytotoxic CD4 cells
274-284
Walton, James A.
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Lydyard, Peter M.
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Nathwani, Amit
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Emery, Vincent
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Akbar, Arne
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Glennie, Martin J.
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Poraskishvili, Nino
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6 November 2009
Walton, James A.
eca504a8-86ed-4340-90a2-67b9289c3cb6
Lydyard, Peter M.
b4520f1b-c89f-4c0a-ab0f-243036b23765
Nathwani, Amit
a244435d-5937-4382-8d43-b9a495d03b27
Emery, Vincent
b2cf9949-78a6-42b8-a919-b61a985e39db
Akbar, Arne
693bdf8c-c20a-4b47-b498-f2d5106b154f
Glennie, Martin J.
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Poraskishvili, Nino
d0e907f7-3170-4a28-a8e6-062ab175b2b7
Walton, James A., Lydyard, Peter M., Nathwani, Amit, Emery, Vincent, Akbar, Arne, Glennie, Martin J. and Poraskishvili, Nino
(2009)
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), .
(doi:10.1111/j.1365-2141.2009.07964.x).
Abstract
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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Published date: 6 November 2009
Keywords:
chronic lymphocytic leukaemia, cytomegalovirus, cytotoxicity, cytotoxic CD4 cells
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Local EPrints ID: 153843
URI: http://eprints.soton.ac.uk/id/eprint/153843
ISSN: 0007-1048
PURE UUID: 830e6524-36fa-41c1-81d9-f11d409938a3
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Date deposited: 21 May 2010 09:17
Last modified: 14 Mar 2024 01:32
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Author:
James A. Walton
Author:
Peter M. Lydyard
Author:
Amit Nathwani
Author:
Vincent Emery
Author:
Arne Akbar
Author:
Martin J. Glennie
Author:
Nino Poraskishvili
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