In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2022-4-22), p. e1010206-
Kurzfassung:
Reconstitution of the T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by stimulation with peptides representing defined epitopes covering multiple HLA restrictions. T cells were adoptively transferred to a patient who had developed persisting high titers of EBV after allogeneic stem cell transplantation for angioimmunoblastic T-cell lymphoma (AITL). T cell receptor beta (TCRβ) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring of T cell clonotypes at a molecular level after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010206
DOI:
10.1371/journal.ppat.1010206.g001
DOI:
10.1371/journal.ppat.1010206.g002
DOI:
10.1371/journal.ppat.1010206.g003
DOI:
10.1371/journal.ppat.1010206.g004
DOI:
10.1371/journal.ppat.1010206.t001
DOI:
10.1371/journal.ppat.1010206.t002
DOI:
10.1371/journal.ppat.1010206.s001
DOI:
10.1371/journal.ppat.1010206.s002
DOI:
10.1371/journal.ppat.1010206.s003
DOI:
10.1371/journal.ppat.1010206.s004
DOI:
10.1371/journal.ppat.1010206.s005
DOI:
10.1371/journal.ppat.1010206.s006
DOI:
10.1371/journal.ppat.1010206.s007
DOI:
10.1371/journal.ppat.1010206.s008
DOI:
10.1371/journal.ppat.1010206.s009
DOI:
10.1371/journal.ppat.1010206.s010
DOI:
10.1371/journal.ppat.1010206.s011
DOI:
10.1371/journal.ppat.1010206.s012
DOI:
10.1371/journal.ppat.1010206.s013
DOI:
10.1371/journal.ppat.1010206.s014
DOI:
10.1371/journal.ppat.1010206.s015
DOI:
10.1371/journal.ppat.1010206.r001
DOI:
10.1371/journal.ppat.1010206.r002
DOI:
10.1371/journal.ppat.1010206.r003
DOI:
10.1371/journal.ppat.1010206.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2205412-1