Advertisement

Generation of human memory stem T cells upon 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 and Chiara Bonini

Key points

  • TSCM lymphocytes are preferentially generated from naïve precursors in vivo early after haploidentical HSCT.

  • TSCM cells represent relevant novel players in the diversification of immunological memory following haploidentical HSCT.

Abstract

Memory stem T cells (TSCM) have been proposed as key determinants of immunological 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 post transplant immune reconstitution in humans. We found that donor-derived TSCM cells are highly enriched early after HSCT. We showed at the antigen-specific and clonal level that TSCM lymphocytes can differentiate directly from naïve precursors infused within the graft and that the extent of TSCM generation might correlate with IL-7 serum levels. In vivo fate mapping through TCR sequencing allowed defining the in vivo differentiation landscapes of human naïve T cells, supporting the notion that progenies of single naïve cells embrace disparate fates in vivo, and highlighting TSCM as relevant novel players in the diversification of immunological memory following allogeneic HSCT.

  • Submitted November 3, 2014.
  • Accepted February 22, 2015.