The number of cytomegalovirus-specific CD4+ T cells is markedly expanded in patients with B-cell chronic lymphocytic leukaemia and determines the total CD4+ T cell repertoire.

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.