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

Blood. 2009 Dec 3;114(24):5071-80. doi: 10.1182/blood-2009-04-214684. Epub 2009 Sep 23.

Abstract

The successful reconstitution of adaptive immunity to human cytomegalovirus (CMV) in hematopoietic stem cell transplantation (HSCT) recipients is central to the reduction of viral reactivation-related 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 epitope-specific 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 during HSCT, which enables the identification of recipients at particular risk of CMV reactivation after HSCT.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptive Immunity*
  • Adolescent
  • Adult
  • Cell Differentiation / immunology
  • Chromatography, High Pressure Liquid
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Memory / immunology
  • Phenotype
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology*
  • Young Adult