Identification of T-cell clones showing expansion associated with graft-vs-leukemia effect on chronic myelogenous leukemia in vivo and in vitro

Objective Although the graft-vs-leukemia (GVL) effect induced by donor leukocyte infusion (DLI) is thought to be mediated by T cells, their features, as well as target molecules, remain unknown. To characterize T cells that mediate the GVL effect on chronic myelogenous leukemia (CML), we studied T-cell repertoire in peripheral blood (PB) of two patients treated with DLI for relapsed CML after allogeneic bone marrow transplantation. Material and Methods Peripheral blood mononuclear cells (PBMCs) were obtained at 2-week intervals following DLI and examined for the presence of antigen-driven T-cell proliferation using complementarity-determining region (CDR) 3 size spectratyping of T-cell receptor β chain subfamilies. Results Both patients exhibited transient proliferation of a limited number of T cells at a certain point in time (day 132 for patient 1 and day 75 for patient 2) after DLI in association with a decrease in the proportion of Philadelphia chromosome (Ph)–positive cells. In patient 2, who showed expansion of a BV16+ T cell in PB, expansion of BV16+ T cells with a similar CDR3 motif containing QDR to that of PB was demonstrated in the bone marrow (BM) sampled on day 33 and in the buccal mucosal tissue, showing chronic graft-vs-host disease (GVHD) on day 138 after DLI. When PBMCs obtained from patient 2 in remission were cultured with cryopreserved CML cells for 2 weeks, proliferation of a BV16+ T cell with a CDR3 motif of QIR was induced in vitro. Conclusion These findings indicate that transient proliferation of a limited number of T cells detected in PB 3–5 months after DLI probably reflects the GVL response against CML cells and may serve as a marker for the appearance of the GVL effect induced by DLI.