Patterns of Cytomegalovirus Reactivation Are Associated with Distinct Evolutive Profiles of Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

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Abstract
Tcell—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.

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