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Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation.
Roberto, Alessandra; Castagna, Luca; Zanon, Veronica; Bramanti, Stefania; Crocchiolo, Roberto; McLaren, James E; Gandolfi, Sara; Tentorio, Paolo; Sarina, Barbara; Timofeeva, Inna; Santoro, Armando; Carlo-Stella, Carmelo; Bruno, Benedetto; Carniti, Cristiana; Corradini, Paolo; Gostick, Emma; Ladell, Kristin; Price, David A; Roederer, Mario; Mavilio, Domenico; Lugli, Enrico.
Affiliation
  • Roberto A; Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;
  • Castagna L; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Zanon V; Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;
  • Bramanti S; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Crocchiolo R; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • McLaren JE; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom;
  • Gandolfi S; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Tentorio P; Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;
  • Sarina B; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Timofeeva I; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Santoro A; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy;
  • Carlo-Stella C; Hematology and Bone Marrow Transplant Unit, Humanitas Cancer Center, Rozzano, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy;
  • Bruno B; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy;
  • Carniti C; Department of Haematology and Pediatric Onco-Haematology, Istituto Nazionale Tumori, Milan, Italy; and.
  • Corradini P; Department of Haematology and Pediatric Onco-Haematology, Istituto Nazionale Tumori, Milan, Italy; and.
  • Gostick E; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom;
  • Ladell K; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom;
  • Price DA; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom;
  • Roederer M; ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Mavilio D; Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy;
  • Lugli E; Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;
Blood ; 125(18): 2855-64, 2015 Apr 30.
Article in En | MEDLINE | ID: mdl-25742699
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. These trials were registered at www.clinicaltrials.gov as #NCT02049424 and #NCT02049580.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stem Cells / T-Lymphocytes / Hematopoietic Stem Cell Transplantation / Lymphopoiesis / Immunologic Memory Limits: Adult / Humans Language: En Journal: Blood Year: 2015 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stem Cells / T-Lymphocytes / Hematopoietic Stem Cell Transplantation / Lymphopoiesis / Immunologic Memory Limits: Adult / Humans Language: En Journal: Blood Year: 2015 Type: Article