Identification of T-cell clones showing expansion associated with graft-vs-leukemia effect on chronic myelogenous leukemia in vivo and in vitro.
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. 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 beta chain subfamilies. 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. 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.
Kondo
Y
Y
Third Department of Medicine, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan 920-8641.
Shiobara
S
S
Nakao
S
S
D000328:Adult; D000595:Amino Acid Sequence; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D005260:Female; D020544:Graft vs Leukemia Effect; D006801:Humans; D016219:Immunotherapy, Adoptive; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D017708:Leukocyte Transfusion; D009061:Mouth Mucosa / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D022801:Complementarity Determining Regions