Distinct Oligoclonal T Cells Are Associated With Graft Versus Host Disease After Stem-Cell Transplantation

Authors:
  • MKMaciej Kmieciak
    Maciej Kmieciak
  • RSRoy T. Sabo
    Roy T. Sabo
  • CRCatherine H. Roberts
    Catherine H. Roberts
  • MIMichael O. Idowu
    Michael O. Idowu
  • KMKatherine Mallory
    Katherine Mallory
  • HCHarold M. Chung
    Harold M. Chung
  • JMJohn M. McCarty
    John M. McCarty
  • CBChristian A. Borrelli
    Christian A. Borrelli
  • MDMichelle M. Detwiler
    Michelle M. Detwiler
  • AKA. Latif Kazim
    A. Latif Kazim
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Abstract
In patients with hematologic malignancies who receive stem-cell transplantation, donors' T cells can recognize minor histocompatibility antigens on recipient cells and generate an objective response against the tumor. However, a major side effect of such therapy is graft-versus-host disease (GVHD). The purpose of this study was to characterize distinct T-cell clones that were frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects. We hypothesized that distinct GVHD-associated T-cell clones can be identified during the disease progression. To test this, we conducted comparative analysis of T-cell receptor (TCR) Vβs in donor-recipient pairs of patients with GVHD versus those with GVHD-free and relapse-free survival using quantitative reverse-transcriptase polymerase chain reaction and spectratyping analyses. We identified three sets of T-cell clones that were either frequently involved in GVHD (TCR Vβ4, 11, and 23) or GVT effect (TCR Vβ9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR Vβ2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR Vβs. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease. These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR Vβ to develop targeted therapy for GVHD.

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