In vitro T-cell receptor V beta repertoire analysis may identify which T-cell V beta families mediate graft-versus-leukaemia and graft-versus-host responses after human leucocyte antigen-matched sibling stem cell transplantation.
We studied oligoclonal T-cell expansions of 24 T-cell receptor (TCR) V beta families in normal donor lymphocytes stimulated with patient's cells and in recipient blood after transplant, using a polymerase chain reaction-based assay (spectratyping). T cells from donor blood were incubated with separated myeloid leukaemia cells or T cells from the HLA-identical sibling recipient. In five of the six patients tested, the T-cell V beta skewing pattern observed in vitro was seen in vivo after transplant. After transplant, the myeloid-specific V beta skewing coincided with the disappearance of residual disease in three patients and in one patient skewing was lost at the time of leukaemic relapse. In functional tests, T cells generated against leukaemic cells in vitro produced interferon gamma in response to the leukaemia. Removal of the leukaemia-expanded skewed V beta families significantly decreased cytotoxic killing of the leukaemia. However, while there was a general concordance in the V beta family exhibiting clonal expansion in vitro and in vivo, the exact clonotype expanded in vitro and in vivo differed. These findings suggest that alloresponses involve multiple T-cell clones within a restricted TCR V beta repertoire that undergo different selection pressures in vitro and in vivo.
Epperson
D E
DE
Bone Marrow Transplant Unit, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Margolis
D A
DA
McOlash
L
L
Janczak
T
T
Barrett
A J
AJ
D000208:Acute Disease; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014184:Transplantation, Homologous
D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma