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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.
- Source :
- British Journal of Haematology; Jan2010, Vol. 148 Issue 2, p274-284, 11p, 1 Chart, 7 Graphs
- Publication Year :
- 2010
-
Abstract
- We have previously shown an expansion of cytotoxic antigen-experienced CD4<superscript>+</superscript>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<superscript>+</superscript>CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4<superscript>+</superscript>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<superscript>+</superscript>PF<superscript>+</superscript> and CD4<superscript>+</superscript>PF<superscript>−</superscript> 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<superscript>+</superscript>PF<superscript>+</superscript>T cell expansion in B-CLL patients and controls was strongly associated with HCMV seropositivity. CD4<superscript>+</superscript>PF<superscript>+</superscript> compared to CD4<superscript>+</superscript>PF<superscript>−</superscript> cells from SP B-CLL patients elicited major histocompatibility complex (MHC) class II-restricted responses to HCMV. CD4<superscript>+</superscript>PF<superscript>+</superscript>T cells from patients and controls were enriched with highly differentiated T-effector/memory (CCR7<superscript>−</superscript>) and revertant (CCR7<superscript>−</superscript>CD45RA<superscript>+</superscript>) phenotype. CD4<superscript>+</superscript>PF<superscript>+</superscript>T cells from B-CLL patients had shorter telomeres than CD4<superscript>+</superscript>PF<superscript>−</superscript>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<superscript>+</superscript>PF<superscript>+</superscript>T cell population with effector/memory phenotype. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANTINEOPLASTIC agents
B cells
LYMPHOCYTIC leukemia
T cells
CYTOMEGALOVIRUS diseases
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 148
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 46823999
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2009.07964.x