Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation.
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 antigen-specific 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 immunological memory after allogeneic HSCT.
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy;
Nicoletta
N
Cieri
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and University Vita-Salute San Raffaele, Milan, Italy;
Giacomo
G
Oliveira
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy;
Raffaella
R
Greco
Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;
Mattia
M
Forcato
Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;
Cristian
C
Taccioli
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and.
Beatrice
B
Cianciotti
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and Molmed S.p.A., Milan, Italy.
Veronica
V
Valtolina
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and.
Maddalena
M
Noviello
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Unit of Molecular and Functional Immunogenetics and.
Luca
L
Vago
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy;
Attilio
A
Bondanza
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;
Francesca
F
Lunghi
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;
Sarah
S
Marktel
Immunohematology and Transfusion Medicine Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; and.
Laura
L
Bellio
University Vita-Salute San Raffaele, Milan, Italy; Molmed S.p.A., Milan, Italy.
Claudio
C
Bordignon
Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;
Silvio
S
Bicciato
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;
Jacopo
J
Peccatori
Hematology and Bone Marrow Transplantation Unit, Department of Oncology, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Unit of Molecular and Functional Immunogenetics and Immunohematology and Transfusion Medicine Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; and.
Fabio
F
Ciceri
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Program in Immunology and Bio-immunotherapy of Cancer and.
Chiara
C
Bonini
D000328:Adult; D001782:Blood Donors; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D038041:Lymphopoiesis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D014184:Transplantation, Homologous
D019408:Platelet Endothelial Cell Adhesion Molecule-1