title: Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation.
abstract: Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor gamma delta+ (TCR gamma delta+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR gamma delta (anti-TCR gamma delta-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCR gamma delta+ cells. Consistent increased numbers of gamma delta cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant gamma delta and alpha beta T cells express the CD45RO antigen, which is usually expressed on "memory" cells only. The V-region usage of the TCR gamma delta+ T cells was analyzed using fresh mononuclear cells and MoAbs against known V gamma and V delta regions. For more detailed analysis, CD3+TCR gamma delta+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly V gamma 9+V delta 1-V delta 2+ cells were found during engraftment. Only after 6 weeks post-BMT, V gamma 9-V delta 1+V delta 2- cells appear. Analysis of the V gamma and V delta usage at the clonal level confirmed the observation that early after BMT only V gamma 9+V delta 2+ cells are present, whereas gamma delta T-cell clones expressing other gamma delta TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of V gamma 9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of V gamma 9+ cells, or (B) selective outgrowth of preexisting V gamma 9+V delta 2+CD45RO+ TCR gamma delta cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.
authors.affiliation: Department of Immunohaematology and Bloodbank, University Hospital, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van der Harst
authors.forename: A
authors.initials: A
authors.lastname: Brand
authors.forename: S A
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Y M
authors.initials: YM
authors.lastname: Kooij-Winkelaar
authors.forename: F E
authors.initials: FE
authors.lastname: Zwaan
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D016026:Bone Marrow Transplantation; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000628:therapy; D017493:Leukocyte Common Antigens; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D006649:Histocompatibility Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017493:Leukocyte Common Antigens