Cytomegalovirus Specific Immunity in Paediatric Cardiac Transplantation

Abstract

Purpose Cytomegalovirus (CMV) disease remains an important risk factor in transplant recipients, particularly in pediatric patients. The role of CMV specific immunity in protecting against viral infection/rebound is yet to be elucidated in the paediatric context. We investigated the relationship between CMV-specific T-cell responses and CMV viral load. We also measured soluble markers of inflammation, such as CX3CL1 (fractalkine), an atypical chemokine with a documented role in the development of numerous inflammatory diseases including atherosclerosis. Methods and Materials Blood samples from 28 heart-transplanted children were taken at 0, 1, 2, 4, and then 4-weekly time points, up to one year. Patients were divided into 3 groups according to CMV exposure (donor or recipient positive) and CMV viral load. Peripheral blood mononuclear cells were assessed for CMV-specific T cell response, and CD57 and Granzyme B was measured. Soluble markers were measured in plasma. Results 7 children had viremia within 12 weeks after transplant. Their CD8+ cells responded to CMV stimulation between 16-32 weeks post-transplant. Patients who had been exposed to CMV, but did not get CMV viremia (n=11), had CMV specific responses within the first 12 weeks post-transplant. CMV specific responses were similar in the CMV exposed groups by one year post transplant. CMV exposed patients showed a slight augmentation in the granzyme B production while those who had viral inactivation/reinfection post-transplant exhibited increased cytotoxic profiles. CMV exposed patients had higher plasma fractalkine levels than CMV negative patients, but patients with viremia appeared to maintain higher levels throughout the first year post-transplant. Conclusions Our data show that CMV specific T cell responses are predictive of CMV viremia. Monitoring of T cell responses can guide immunosuppression and thus may reduce CMV disease post transplant. The demonstration of elevated fractalkine further illustrated the potential of CMV to propagate coronary allograft vasculopathy.