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

Scheinberg, Phillip, Melenhorst, Jan J., Brenchley, Jason M., Hill, Brenna J., Hensel, Nancy F., Chattopadhyay, Pratip K., Roederer, Mario, Picker, Louis J., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Barrett, A. John and Douek, Daniel C. 2009. 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 114 (24) , pp. 5071-5080. 10.1182/blood-2009-04-214684

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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.

Item Type:	Article
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Society of Hematology
ISSN:	0006-4971
Last Modified:	20 Oct 2022 08:25
URI:	https://orca.cardiff.ac.uk/id/eprint/28232

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