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Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide
Christopher G. Kanakry, … , Leo Luznik, Edus H. Warren
Christopher G. Kanakry, … , Leo Luznik, Edus H. Warren
Published April 21, 2016
Citation Information: JCI Insight. 2016;1(5):e86252. https://doi.org/10.1172/jci.insight.86252.
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Categories: Research Article Immunology Oncology

Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide

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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 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.

Authors

Christopher G. Kanakry, David G. Coffey, Andrea M.H. Towlerton, Ante Vulic, Barry E. Storer, Jeffrey Chou, Cecilia C.S. Yeung, Christopher D. Gocke, Harlan S. Robins, Paul V. O’Donnell, Leo Luznik, Edus H. Warren

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Figure 1

The association of clinical factors with lymphocyte recovery after myeloablative, HLA-matched alloBMT using PTCy as single-agent GVHD prophylaxis.

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The association of clinical factors with lymphocyte recovery after myelo...
Numerical reconstitution of lymphocytes, CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3–CD56+ NK cells, and CD19+ B cells is shown for (A) all patients and donors and stratified by (B) recipient cytomegalovirus (CMV) serostatus, (C) the detection of peripheral blood CMV reactivation after transplant occurring by the specified time point, or (D) the diagnosis of acute graft-versus-host disease (GVHD) by the specified time point. Error bars represent the standard error. Donor data in B are stratified by donor CMV serostatus. Donor and pretransplant recipient data are shown in D for comparison purposes only.
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