The Lack and Cytomegalovirus-Specific Cellular Immune Response May Contribute to the Onset of Organ Infection and Disease in Lung Transplant Recipients

Abstract

Cellular immune response has been demonstrated to play a role in the control of human cytomegalovirus (HCMV) replication in organ transplant recipients. Herein, HCMV-specific T-cell response and association to the onset of organ infection/disease were prospectively evaluated by EliSPOT assay in a population of 46 lung transplant (LT) recipients at 1, 3, 6, 9 and 12 months post-transplantation. According to our centre's practice, a combined prolonged antiviral prophylaxis (HCMV-IG for 12 months and ganciclovir or valganciclovir for 3 weeks from postoperative day 21) was given to all LT recipients. HCMV-DNA was concomitantly detected on bronchoalveolar lavage (BAL) and whole blood by real-time PCR. Approximately one third of patients resulted HCMV persistently non-responder; the rate of HCMV infection, as evaluated by HCMV-DNA positivity, tended to be higher in non-responders. Mean viral load on BAL was significantly higher in non-responders vs other patients (p <0.001). Temporal profile of infections appeared related to the HCMV responder status with a shorter time to onset of infection post-transplantation and a longer duration in non-responders. The occurrence of organ disease (i.e. pneumonia) tended to be higher in non-responders, with poor prognosis, as death occurred in one of three non-responder patients that developed HCMV pneumonia. The lack of HCMV-specific cellular response can contribute to the onset of organ infection and disease also in patients in which antiviral prophylaxis was adopted; this could be due to the potential occurrence of incomplete control of replication in lungs or a delayed priming of T-cell reconstitution.