骨髓移植后早期CD45RO+Vγ9+/Vδ2+T细胞受体γ/δT细胞的选择性增殖。

Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation.

作者信息

van der Harst D, Brand A, van Luxemburg-Heijs S A, Kooij-Winkelaar Y M, Zwaan F E, Koning F

机构信息

Department of Immunohaematology and Bloodbank, University Hospital, Leiden, The Netherlands.

出版信息

Blood. 1991 Oct 1;78(7):1875-81.

PMID:1832995

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.

摘要

在对血液系统恶性肿瘤患者进行骨髓移植（BMT）前后，采集了10例患者的外周血单个核细胞。通过针对CD3和T细胞受体γδ（抗-TCRγδ-1）的单克隆抗体（MoAbs）反应，确定了CD3⁺T细胞受体γδ⁺（TCRγδ⁺）细胞的相对数量和绝对数量。移植前，9例接受检测的患者中有8例的CD3⁺TCRγδ⁺细胞少于10%。在BMT后的前4个月内，9例接受检测的患者中有4例可见γδ细胞数量持续增加，最多可达移植前水平的8倍。移植后早期的绝大多数γδ和αβT细胞表达CD45RO抗原，该抗原通常仅在“记忆”细胞上表达。使用新鲜的单个核细胞和针对已知Vγ和Vδ区域的MoAbs分析TCRγδ⁺T细胞的V区使用情况。为了进行更详细的分析，对CD3⁺TCRγδ⁺细胞进行分选，进行大量培养和克隆。使用新鲜细胞和大量培养物，在植入过程中主要发现Vγ9⁺Vδ1⁻Vδ2⁺细胞。仅在BMT后6周，Vγ9⁻Vδ1⁺Vδ2⁻细胞才出现。在克隆水平上对Vγ和Vδ使用情况的分析证实了以下观察结果：BMT后早期仅存在Vγ9⁺Vδ2⁺细胞，而表达其他γδTCR表型的γδT细胞克隆仅在BMT后4至6周才能检测到。早期植入过程中Vγ9⁺细胞占优势可能由多种机制解释：（A）T细胞发育过程中的顺序重排，导致早期出现一波Vγ9⁺细胞，或（B）骨髓移植物中预先存在的Vγ9⁺Vδ2⁺CD45RO⁺TCRγδ细胞的选择性生长，这可能是由于接触环境抗原导致抗原驱动的扩增所致。