title: The number of cytomegalovirus-specific CD4+ T cells is markedly expanded in patients with B-cell chronic lymphocytic leukemia and determines the total CD4+ T-cell repertoire.
abstract: B-cell chronic lymphocytic leukemia is associated with immune suppression and an altered T-cell repertoire with expansion of memory cells. Cytomegalovirus (CMV) is a common herpes virus that elicits a strong virus-specific T-cell immune response after infection. We studied the CMV-specific CD4(+) T-cell response in 45 patients and 35 control subjects and demonstrated that it was markedly expanded in the patient group, averaging 11% of the CD4(+) pool compared with 4.7% in controls. The magnitude of the CMV-specific CD4(+) immune response increased with disease stage and was particularly high in patients who received chemotherapy. Within this group, the CMV-specific response comprised over 46% of the CD4(+) T-cell repertoire in some patients. Serial analysis revealed that CMV-specific immunity increased during treatment with chemotherapy and remained stable thereafter. CMV-seropositive patients exhibited a markedly altered CD4(+) T-cell repertoire with increased numbers of CD45R0(+) T cells and a reduction in CD27, CD28, and CCR7 expression. Overall survival was reduced by nearly 4 years in CMV-seropositive patients, although this did not reach statistical significance. CLL patients therefore demonstrate an expansion of the CD4(+) CMV-specific immune response, which is likely to contribute to the immunological and clinical features of this disease.
authors.affiliation: School for Cancer Sciences, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Batoul
authors.initials: B
authors.lastname: Pourgheysari
authors.forename: Rachel
authors.initials: R
authors.lastname: Bruton
authors.forename: Helen
authors.initials: H
authors.lastname: Parry
authors.forename: Lucinda
authors.initials: L
authors.lastname: Billingham
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Jim
authors.initials: J
authors.lastname: Murray
authors.forename: Paul
authors.initials: P
authors.lastname: Moss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002452:Cell Count; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged
chemical_list: D017252:CD3 Complex