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

Phillip Scheinberg, Jan J. Melenhorst, Jason M. Brenchley, Brenna J. Hill, Nancy F. Hensel, Pratip K. Chattopadhyay, Mario Roederer, Louis Picker, David A. Price, A. John Barrett, Daniel C. Douek

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)5071-5080
Number of pages10
JournalBlood
Volume114
Issue number24
DOIs
StatePublished - Dec 3 2009

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T-cells
Hematopoietic Stem Cell Transplantation
Adaptive Immunity
Stem cells
Cytomegalovirus
T-Lymphocytes
Phenotype
Data storage equipment
Adoptive Transfer
Immunologic Factors
Immunity
Maintenance
Morbidity
Antigens
Mortality
Chemical analysis

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Scheinberg, P., Melenhorst, J. J., Brenchley, J. M., Hill, B. J., Hensel, N. F., Chattopadhyay, P. K., ... Douek, D. C. (2009). 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. Blood, 114(24), 5071-5080. https://doi.org/10.1182/blood-2009-04-214684

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. / Scheinberg, Phillip; Melenhorst, Jan J.; Brenchley, Jason M.; Hill, Brenna J.; Hensel, Nancy F.; Chattopadhyay, Pratip K.; Roederer, Mario; Picker, Louis; Price, David A.; Barrett, A. John; Douek, Daniel C.

In: Blood, Vol. 114, No. 24, 03.12.2009, p. 5071-5080.

Research output: Contribution to journalArticle

Scheinberg, P, Melenhorst, JJ, Brenchley, JM, Hill, BJ, Hensel, NF, Chattopadhyay, PK, Roederer, M, Picker, L, Price, DA, Barrett, AJ & Douek, DC 2009, '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', Blood, vol. 114, no. 24, pp. 5071-5080. https://doi.org/10.1182/blood-2009-04-214684
Scheinberg, Phillip ; Melenhorst, Jan J. ; Brenchley, Jason M. ; Hill, Brenna J. ; Hensel, Nancy F. ; Chattopadhyay, Pratip K. ; Roederer, Mario ; Picker, Louis ; Price, David A. ; Barrett, A. John ; Douek, Daniel C. / 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. In: Blood. 2009 ; Vol. 114, No. 24. pp. 5071-5080.
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