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

S Buhler, F Bettens, C Dantin, S Ferrari-Lacraz… - Leukemia, 2020 - nature.com
S Buhler, F Bettens, C Dantin, S Ferrari-Lacraz, M Ansari, AC Mamez, S Masouridi-Levrat…
Leukemia, 2020nature.com
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 …
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.
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