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

Roberto, A., Castagna, L., Zanon, V., Bramanti, S., Crocchiolo, R., McLaren, James Edward, Gandolfi, S., Tentorio, P., Sarina, B., Timofeeva, I., Santoro, A., Carlo-Stella, C., Bruno, B., Carniti, C., Corradini, P., Gostick, Emma, Ladell, Kristin Ingrid, Price, David, Roederer, M., Mavilio, D. and Lugli, E. 2015. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 125 (18) , pp. 2855-2864. 10.1182/blood-2014-11-608406

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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 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 naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Society of Hematology
ISSN: 0006-4971
Date of Acceptance: 28 February 2015
Last Modified: 04 Jun 2017 08:47
URI: http://orca.cf.ac.uk/id/eprint/84810

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