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Leukemia. 2019 Nov 26. doi: 10.1038/s41375-019-0654-y. [Epub ahead of print]

Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation.

Author information

1
Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. stephane.buhler@hcuge.ch.
2
Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland.
3
Service of Haematology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
4
Pediatric Department, Onco-Hematology Unit, Geneva University Hospitals and Cansearch research laboratory, Geneva Medical School, Geneva, Switzerland.
5
Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. jean.villard@hcuge.ch.

Abstract

After allogeneic hematopoietic stem cell transplantation (HSCT), immune reconstitution leads to the development of a new T-cell repertoire. Immune reconstitution could be influenced by events such as conditioning, infections, and graft versus host disease (GVHD). Factors influencing the TCR diversity are of great interest to fine-tune the strategy for donor selection and to optimize standard of care. In this work, immunosequencing of the TCR CDR3β region was carried out in a large cohort of 116 full chimeric recipients at 1 year post-HSCT and their respective donors prior to transplantation. The repertoire overlap before and after HSCT was minimal, supporting de novo reconstitution as a primary pathway at any age. Among the parameters investigated, increased patient and/or donor age as well as positive CMV serologic status reinforced by CMV infection/reactivation were the ones significantly associated with a reduced diversity at 1 year post-HSCT. CMV-specific T-cell clones were shown to influence the clonality of the repertoire alongside the expansion of limited numbers of non-CMV T-cell populations. Interestingly, at the exception of CMV infection/reactivation, TCR diversity was not predictive of GVHD, relapse, death, or infections post-HSCT.

PMID:
31772297
DOI:
10.1038/s41375-019-0654-y

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