TY - JOUR
T1 - Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation
AU - Cieri, Nicoletta
AU - Oliveira, Giacomo
AU - Greco, Raffaella
AU - Forcato, Mattia
AU - Taccioli, Cristian
AU - Cianciotti, Beatrice
AU - Valtolina, Veronica
AU - Noviello, Maddalena
AU - Vago, Luca
AU - Bondanza, Attilio
AU - Lunghi, Francesca
AU - Marktel, Sarah
AU - Bellio, Laura
AU - Bordignon, Claudio
AU - Bicciato, Silvio
AU - Peccatori, Jacopo
AU - Ciceri, Fabio
AU - Bonini, Chiara
PY - 2015/4/30
Y1 - 2015/4/30
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84928789921&partnerID=8YFLogxK
U2 - 10.1182/blood-2014-11-608539
DO - 10.1182/blood-2014-11-608539
M3 - Article
C2 - 25736310
AN - SCOPUS:84928789921
VL - 125
SP - 2865
EP - 2874
JO - Blood
JF - Blood
SN - 0006-4971
IS - 18
ER -