Early T cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Post-transplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated 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 naïve, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that post-transplant TSCM cells originate from naïve precursors. Moreover, donor naïve 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 generated 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 naïve-derived TSCM cells in the clinical setting to overcome immunodeficiency.
Role of naïve-derived T memory stem cells in T cell reconstitution following allogeneic transplantation / A. Roberto, L. Castagna, V. Zanon, S. Bramanti, R. Crocchiolo, J.E. Mclaren, S. Gandolfi, P. Tentorio, B. Sarina, I. Timofeeva, A. Santoro, C. Carlo-Stella, B. Bruno, C. Carniti, P. Corradini, E. Gostick, K. Ladell, D.A. Price, M. Roederer, D. Mavilio, E. Lugli. - In: BLOOD. - ISSN 0006-4971. - 125:18(2015 Apr 30), pp. 2855-2864. [10.1182/blood-2014-11-608406]
Role of naïve-derived T memory stem cells in T cell reconstitution following allogeneic transplantation
V. Zanon;S. Bramanti;S. Gandolfi;C. Carlo-Stella;P. Corradini;D. Mavilio;
2015
Abstract
Early T cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Post-transplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated 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 naïve, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that post-transplant TSCM cells originate from naïve precursors. Moreover, donor naïve 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 generated 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 naïve-derived TSCM cells in the clinical setting to overcome immunodeficiency.File | Dimensione | Formato | |
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