Levels of cytomegalovirus-specific CD4+ T cells are markedly expanded in patients with B-cell chronic lymphocytic leukaemia and determine the total CD4+ T cell repertoire

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BlankBlood First Edition Paper, prepublished online June 18, 2010; DOI

10.1182/blood-2009-12-257147.

Levels of cytomegalovirus-specific CD4+ T cells are markedly expanded in

patients with B-cell chronic lymphocytic leukaemia and determine the total CD4+

T cell repertoire

Batoul Pourgheysari1, Bruton1, Helen Parry1, Lucinda Billingham1, Chris

Fegan2, Jim Murray3 and Moss1,*

1 School of Cancer Sciences, University of Birmingham, Birmingham, United

Kingdom; 2 Department of Haematology, School of Medicine, Cardiff University,

Cardiff, United Kingdom; 3 Department of Haematology, University Hospitals NHS

Foundation Trust, Birmingham, United Kingdom

* Corresponding author; email: p.moss@...

Abstract

B-cell chronic lymphocytic leukaemia is associated with immune suppression and

an altered T cell repertoire with expansion of memory cells. Cytomegalovirus 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 demonstrate it to be markedly expanded in

the patient group, averaging 11% of the total CD4+ pool compared to 4.7% in

controls. The magnitude of the CMV-specific CD4+ immune response increased with

disease stage and was particularly high in patients who had 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