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.