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Stem cell transplantation

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

Leukemia volume 34, pages 1422–1432 (2020)Cite this article

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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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Acknowledgements

This study was supported by the Swiss National Science Foundation (grant #310030_173237/1), the Academic Society of the University of Geneva, IRGHET (International Research Group on unrelated Hematopoietic stem cell Transplantation), the Dr Henri Dubois-Ferrière Dinu Lippatti foundation and the Philantropy Settlement. The authors are grateful to Lydie Brunet for her technical expertize and to the technicians of the LNRH for their most efficient support for HLA typing. We would also like to thanks Dr José Manuel Nunes (Biosc-iGE3) for his valuable suggestions on data analysis using R.

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  1. Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland

    Stéphane Buhler, Florence Bettens, Sylvie Ferrari-Lacraz & Jean Villard

  2. Service of Haematology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Carole Dantin, Anne-Claire Mamez, Stavroula Masouridi-Levrat & Yves Chalandon

  3. Pediatric Department, Onco-Hematology Unit, Geneva University Hospitals and Cansearch research laboratory, Geneva Medical School, Geneva, Switzerland

    Marc Ansari

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Buhler, S., Bettens, F., Dantin, C. et al. Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation. Leukemia 34, 1422–1432 (2020). https://doi.org/10.1038/s41375-019-0654-y

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