Selective Outgrowth of CD45RO+ Vγ9+/Vδ2+ T-Cell Receptor γ/δ T Cells Early After Bone Marrow Transplantation

Abstract

AbstractBefore 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 γδ+ (TCRγδ+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR γδ (anti-TCRγδ-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCRγδ+ cells. Consistent increased numbers of γδ cells up to eightfold the pretrans-plant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant γδ and αβ T cells express the CD45RO antigen, which is usually expressed on “memory” cells only. The V-region usage of the TCRγδ+ T cells was analyzed using fresh mononuclear cells and MoAbs against known Vγ and Vδ regions. For more detailed analysis, CD3+TCRγδ+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly Vγ9+Vδ1−Vδ2+ cells were found during engraftment. Only after 6 weeks post-BMT, Vγ9−Vδ1+Vδ2−cells appear. Analysis of the Vγ and Vδ usage at the clonal level confirmed the observation that early after BMT only Vγ9+Vδ2+ cells are present, whereas γδ T-cell clones expressing other γδ TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of Vγ9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of Vγ9+ cells, or (B) selective outgrowth of preexisting Vγ9+Vδ2+CD45RO+ TCRγδ cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.