The transfer of adaptive immunity to CMVduring hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor

The successful reconstitution of adaptive immunity to human cytomegalovirus (CMV) in hematopoietic stem cell transplantation (HSCT) recipients is central to the reduction of viral reactivationrelated morbidity and mortality. Here, we characterized the magnitude, specificity, phenotype, function, and clonotypic composition of CMV-specific T-cell responses in 18 donor-recipient pairs both before and after HSCT. The principal findings were: (1) the specificity of CMV-specific T-cell responses in the recipient after HSCT mirrors that in the donor; (2) the maintenance of these targeting patterns reflects the transfer of epitopespecific T-cell clonotypes from donor to recipient; (3) less differentiated CD27⁺CD57^- CMV-specific memory T cells are more likely to persist in the recipient after HSCT compared with more terminally differentiated CD27^- CD57⁺CMV-specific memory T cells; (4) the presence of greater numbers of less differentiated CD8⁺ CMV-specific T cells in the donor appears to confer protection against viral reactivation in the recipient after HSCT; and (5) CMV-specific T cells acquire a more differentiated phenotype and a restricted functional profile after HSCT. Overall, these findings define the immunologic factors that influence the successful adoptive transfer of antigen-specific T-cell immunity duringHSCT, which enables the identification of recipients at particular risk of CMV reactivation after HSCT.