Patterns of cytomegalovirus reactivation are associated with distinct evolutive profiles of immune reconstitution after allogeneic hematopoietic stem cell transplantation

Abstract

T cell-mediated immunity is essential for the control of cytomegalovirus (CMV) infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify patterns of CMV-specific immune responses associated with multiple or prolonged reactivations. We analyzed findings in 116 recipients during the course of infection or reactivation and latency. CD8(+) T cell responses were determined weekly, using HLA class I tetramers together with extended phenotypic analyses. Our results confirmed that recipients of allo-HSCT from unrelated donors were more susceptible to multiple reactivations and that the donor's CMV serological status influenced the occurrence of prolonged reactivations. We found that a lack of CMV-specific T cells after the first episode of reactivation was associated with multiple subsequent reactivations. In patients with uncontrolled reactivations, CMV-specific T cells of the late differentiation phenotype CD45RA(+)CD27(-)CD28(-) did not develop. Longitudinal evaluation of CD27 and CD45RA expression within the tetramer-positive subset could help identify patients in whom a protective immune response is developing. Evaluation of CMV-specific immune responses during the first episode of reactivation, together with extended phenotypes, could thus improve immune monitoring, especially in recipients at risk of uncontrolled viral reactivation.