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

Leukemia. 2020 May;34(5):1422-1432. doi: 10.1038/s41375-019-0654-y. Epub 2019 Nov 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / genetics
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / genetics
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Receptors, Antigen, T-Cell / genetics*
  • Tissue Donors / supply & distribution
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Virus Activation
  • Young Adult

Substances

  • Receptors, Antigen, T-Cell