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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. Br J Haematol 2001 Jul;114(1):57-62

Date

07/27/2001

Pubmed ID

11472345

DOI

10.1046/j.1365-2141.2001.02879.x

Scopus ID

2-s2.0-0034934630   18 Citations

Abstract

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.

Author List

Epperson DE, Margolis DA, McOlash L, Janczak T, Barrett AJ

Author

David A. Margolis MD Interim Chair, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Disease
Coculture Techniques
Cytotoxicity Tests, Immunologic
Graft vs Host Disease
Graft vs Leukemia Effect
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Interferon-gamma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Polymerase Chain Reaction
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
Transplantation, Homologous