title: Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide.
abstract: Posttransplantation cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD), but its immunologic impact is poorly understood. We assessed lymphocyte reconstitution via flow cytometry (n= 74) and antigen receptor sequencing (n= 35) in recipients of myeloablative, HLA-matched allogeneic BM transplantation using PTCy. Recovering T cells were primarily phenotypically effector memory with lower T cell receptor β (TRB) repertoire diversity than input donor repertoires. Recovering B cells were predominantly naive with immunoglobulin heavy chain locus (IGH) repertoire diversity similar to donors. Numerical T cell reconstitution andTRBdiversity were strongly associated with recipient cytomegalovirus seropositivity. Global similarity between input donor and recipient posttransplant repertoires was uniformly low at 1-2 months after transplant but increased over the balance of the first posttransplant year. BloodTRBrepertoires at ≥3 months after transplant were often dominated by clones present in the donor blood/marrow memory CD8+compartment. Limited overlap was observed between theTRBrepertoires of T cells infiltrating the skin or gastrointestinal tract versus the blood. Although publicTRBsequences associated with herpesvirus- or alloantigen-specific CD8+T cells were detected in some patients, posttransplantTRBandIGHrepertoires were unique to each individual. These data define the immune dynamics occurring after PTCy and establish a benchmark against which immune recovery after other transplantation approaches can be compared.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kanakry
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Coffey
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA.
authors.forename: Andrea M H
authors.initials: AM
authors.lastname: Towlerton
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ante
authors.initials: A
authors.lastname: Vulic
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chou
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA; Department of Pathology, University of Washington, Seattle, Washington, USA.
authors.forename: Cecilia C S
authors.initials: CC
authors.lastname: Yeung
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
authors.affiliation: Public Health Sciences Division, FHCRC, Seattle, Washington, USA.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren