Masuko K, Kato S, Hagihara M, Tsuchida F, Takemoto Y, Izawa K, Kato T, Yamamori S, Mizushima Y, Nishioka K, Tsuji K, Yamamoto K
Division of Rheumatology and Molecular Immunology, St. Marianne University, Kanagawa, Japan.
Blood. 1996 Jan 15;87(2):789-99.
The immune mechanisms of T cells regeneration after bone marrow transplantation (BMT) and the factors maintaining allogeneic marrow graft in the host are still unknown. To pursue this issue, we analyzed T-cell clonality of peripheral blood lymphocytes (PBLs) in BMT recipients, using reverse transcription polymerase chain reaction with T-cell receptor (TCR) V beta gene segment-specific primers and single-strand conformation polymorphism. PBLs from patients and donors showed a heterogeneous T-cell population with oligoclonal accumulations of CD8+ T cells. When PBLs were cultured in HLA-matched mixed lymphocytes reaction in vitro, no distinct clonal expansion was observed. However, after BMT, oligoclonal expansions were induced in the recipients in vivo, without a restriction of TCR V beta gene usage. Although part of the expansion was transient, the majority was repeatedly detected even several months later. Our results suggested that certain in vivo mechanisms maintain a stable clonal expansion of distinct T cells in marrow recipients. We also found in a single patient with graft-versus-host disease a replacement of expanded clones by other clones during follow-up. Diminishing numbers of accumulation clones were found in long-term marrow recipients, indicating a general tendency for clonal expansion to subside progressively. Considered together, our data suggest the involvement of clonally expanded T cells in lymphoid regeneration and in acute and chronic immune responses after BMT.
骨髓移植（BMT）后T细胞再生的免疫机制以及宿主中维持异基因骨髓移植的因素仍然未知。为了探究这个问题，我们使用针对T细胞受体（TCR）Vβ基因片段的特异性引物，通过逆转录聚合酶链反应和单链构象多态性分析了BMT受者外周血淋巴细胞（PBL）的T细胞克隆性。患者和供者的PBL显示出异质性T细胞群体，其中CD8 + T细胞有寡克隆积累。当PBL在体外进行HLA匹配的混合淋巴细胞反应培养时，未观察到明显的克隆扩增。然而，BMT后，受者体内诱导了寡克隆扩增，且不受TCR Vβ基因使用的限制。虽然部分扩增是短暂的，但即使在几个月后，大多数仍能反复检测到。我们的结果表明，某些体内机制维持了骨髓受者中特定T细胞的稳定克隆扩增。我们还在一名患有移植物抗宿主病的患者中发现，随访期间扩增的克隆被其他克隆所取代。在长期骨髓受者中发现积累克隆的数量减少，表明克隆扩增总体上有逐渐消退的趋势。综合考虑，我们的数据表明克隆扩增的T细胞参与了BMT后的淋巴细胞再生以及急性和慢性免疫反应。
