Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide
| Autor: | David G. Coffey, Andrea M. H. Towlerton, Leo Luznik, Christopher G. Kanakry, Harlan Robins, Jeffrey Chou, Barry E. Storer, Christopher D. Gocke, Edus H. Warren, Paul O'Donnell, Cecilia C.S. Yeung, Ante Vulic |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.diagnostic_test Cyclophosphamide T cell Lymphocyte T-cell receptor General Medicine Biology Flow cytometry Transplantation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system medicine.anatomical_structure Immunology medicine CD8 030215 immunology medicine.drug Research Article |
| Popis: | 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 and TRB diversity 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. Blood TRB repertoires at ≥3 months after transplant were often dominated by clones present in the donor blood/marrow memory CD8+ compartment. Limited overlap was observed between the TRB repertoires of T cells infiltrating the skin or gastrointestinal tract versus the blood. Although public TRB sequences associated with herpesvirus- or alloantigen-specific CD8+ T cells were detected in some patients, posttransplant TRB and IGH repertoires 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. |
| Databáze: | OpenAIRE |
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