Ex Vivo Monitoring of Human Cytomegalovirus-Specific CD8+ T-Cell Responses Using the QuantiFERON®-CMV Assay in Allogeneic Hematopoietic Stem Cell Transplant Recipients Attending an Irish Hospital

Reconstitution of human cytomegalovirus (HCMV) T-cell immunity is crucial in hematopoietic stem cell transplant (HSCT) recipients. The OuantiFERON®-CMV assay for cellular HCMV-specific immunity was evaluated in allogeneic HSCT recipients (n=43) and patients with hematological malignancies (n=29) attending a tertiary-care Irish hospital. An intracellular cytokine (ICC) assay correlated with the QuantiFERON®-CMV assay. Although there was agreement between HCMV seropositivity and OuantiFERON®-CMV assay, six HCMV seropositive immunosuppressed patients with hematological malignancy had negative Quanti-FERON®-CMV results. The 43 HSCT recipients were classified as high risk (D―/R+) (n=18), intermediate risk (D+/R+ and D+/R―) (n=17), and low risk (D―/R―) (n=8). During episodes of HCMV DNAemia no evidence of HCMV-specific immunity was found using the Quanti-FERON®-CMV assay. Furthermore, the recovery of HCMV-specific CD8+ T-cell responses in high-risk seropositive recipients of matched unrelated donors was severely delayed, a mean of 200 (SD = 117) days compared to 58 (SD = 23) days for sibling donors (P≤0.028). In addition, three patients with late HCMV infection (infection >100 days post-transplant) had delayed reconstitution of HCMV-specific CD8+ T cells. Interestingly, two recipients (R+/D―) developed rapid immune reconstitution by days 15 and 36 post-HSCT, suggesting HCMV-specific T-cell lymphopoiesis of recipient origin. Levels of CD8+ T-cell immunity in HCMV seropositive HSCT recipients were lowest following HSCT. A high number (33%) of indeterminate results was observed immediately after transplantation. Patients with indeterminate QuantiFERON®-CMV results had low levels of HCMV-specific CD8+ T cells.