title: Induction of HA-1-specific cytotoxic T-cell clones parallels the therapeutic effect of donor lymphocyte infusion.
abstract: Donor lymphocyte infusions (DLI) can induce a graft-versus-leukaemia (GvL) reaction in patients with relapsed disease. However, the mechanisms involved in remission induction are not completely known. A patient with chemotherapy-refractory relapse 1 year after human leucocyte antigen (HLA)-identical, unrelated stem cell transplantation (SCT) for bcr/abl-positive common acute lymphoblastic leukaemia (ALL) received a DLI from the original donor, and achieved complete cytogenetic and molecular remission concomitantly with extensive graft-versus-host disease (GvHD). Seven CD8+, donor-derived, alloreactive T-cell clones were generated by stimulating post-DLI remission cells with the patient's pretransplant mature dendritic cells. The minor histocompatibility antigen (mHag) recognized by these T-cell clones was identified as HA-1, a mHag associated with acute GvHD after SCT. Our finding provides evidence of HA-1-associated GvL effects after DLI that paralleled the eradication of full-blown, chemotherapy-refractory ALL relapse after allogeneic SCT.
authors.affiliation: Laboratory for Tumour- and Immunobiology, Bone Marrow Transplant Unit, Division of Haematology and Oncology, Department of Internal Medicine, Innsbruck University Hospital, Anichstrasse 35, 6020 Innsbruck, Austria. brigitte.eibl@uklibk.ac.at
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kircher
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Martina
authors.initials: M
authors.lastname: Urbanek
authors.forename: Andrea
authors.initials: A
authors.lastname: Mitterschiffthaler
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Kurt
authors.initials: K
authors.lastname: Grünewald
authors.forename: Günther
authors.initials: G
authors.lastname: Gastl
authors.forename: David
authors.initials: D
authors.lastname: Nachbaur
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000601:surgery*; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides