Distinct oligoclonal T cells are associated with graft versus host disease after stem-cell transplantation.

Background. 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. Methods. 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) V beta s 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. Results. We identified three sets of T-cell clones that were either frequently involved in GVHD(TCR V beta 4, 11, and 23) or GVT effect (TCR V beta 9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR V beta 2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR V beta s. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease. Conclusions. These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR V beta to develop targeted therapy for GVHD.