Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation

Alessandra Roberto, Luca Castagna, Veronica Zanon, Stefania Bramanti, Roberto Crocchiolo, James E. McLaren, Sara Gandolfi, Paolo Tentorio, Barbara Sarina, Inna Timofeeva, Armando Santoro, Carmelo Carlo-Stella, Benedetto Bruno, Cristiana Carniti, Paolo Corradini, Emma Gostick, Kristin Ladell, David A. Price, Mario Roederer, Domenico MavilioEnrico Lugli

Research output: Contribution to journalArticle

Abstract

Early T-cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipu-lated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following haploidentical transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttrans-plant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency.

Original languageEnglish
Pages (from-to)2855-2864
Number of pages10
JournalBlood
Volume125
Issue number18
DOIs
Publication statusPublished - Apr 30 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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