Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

Nicoletta Cieri, Giacomo Oliveira, Raffaella Greco, Mattia Forcato, Cristian Taccioli, Beatrice Cianciotti, Veronica Valtolina, Maddalena Noviello, Luca Vago, Attilio Bondanza, Francesca Lunghi, Sarah Marktel, Laura Bellio, Claudio Bordignon, Silvio Bicciato, Jacopo Peccatori, Fabio Ciceri, Chiara Bonini

Research output: Contribution to journalArticlepeer-review

Abstract

Memory stem T cells (TSCM) have been proposed as key determinants of immunologic memory. However, their exact contribution to a mounting immune response, as well as the mechanisms and timing of their in vivo generation, are poorly understood. We longitudinally tracked TSCM dynamics in patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), thereby providing novel hints on the contribution of this subset to posttransplant immune reconstitution in humans. We found that donor-derived TSCM are highly enriched early after HSCT. We showed at the antigenspecific and clonal level that TSCM lymphocytes can differentiate directly from naive precursors infused within the graft and that the extent of TSCM generation might correlate with interleukin 7 serum levels. In vivo fate mapping through T-cell receptor sequencing allowed defining the in vivo differentiation landscapes of human naive T cells, supporting the notion that progenies of single naive cells embrace disparate fates in vivo and highlighting TSCM as relevant novel players in the diversification of immunologicalmemory after allogeneic HSCT.

Original languageEnglish
Pages (from-to)2865-2874
Number of pages10
JournalBlood
Volume125
Issue number18
DOIs
Publication statusPublished - Apr 30 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

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