Analysis of T-cell clone indicating GVL effect due to allo stem cell transplantation and donor lymphocytes infusion.

T 细胞克隆分析表明同种异体干细胞移植和供体淋巴细胞输注产生 GVL 效应。

• 批准号: 10670975
• 负责人: KIMURA Nobuhiro
• 金额: $ 1.73万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670975/
• 关键词: Vβ repertoire; Donor lymphocytes infusion; Allo-BMT; T-cell receptor; Graft versus leukemia; T cell recepton; TCR

Several reports have demonstrated the persistent detection of AML1/MTG8 fusion products, representing minimal residual disease (MRD), in patients with t(8 ; 21) acute myelogenous leukemia (AML) who are in long-term remission. It is probable that immune-mediated mechanisms that are able to suppress the expansion of MRD may result in the continuance of remission. It was previously shown that some t(8 ; 21) AML patients had high anti-MTG8 antibody titers. MTG8 expression in normal adult tissue is either not detectable or else only faintly detectable. We made the hypothesis that the orverexpression of the MTG8 gene in t(8 ; 21) AML cells could act as a possible tumor antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b aa182-191) using monocyte-derived dendritic cells from a healthy donor. T cell receptor (TCR) Vα17, TCRVβ14 and 15 and TCR … More Jβ2.1 and predominantly used in these CTL lines. Our data which suggest that the MTG8 protein could be one of the tumor antigens recognized by CTLs may be helpful in further investigations of TCR analysis in t(8 ; 21) AML patients with HLA-A0201 who are in long-term remission.Hematologic relapse of chronic myeloid leukemia (CML) developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte infusion (DLI) twice at a dose of 5x10ィイD16ィエD1/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLI, and has remained in a CCR state for 17 months. Neither acute chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the TCR repertoire disclosed oligoclonal of T cells of the TCR Vβ and Jβ subfamilies. These observed provide evidence for the clonal expansion of allogeneic T cells that are capable of mediation antileukemic activity without causing GVHD. Less

一些报道表明，在长期缓解的t（8; 21）急性髓性白血病（AML）患者中，AML1/MTG8融合产物持续检测，代表微小残留病（MRD）。这是可能的免疫介导的机制，能够抑制MRD的扩大可能导致缓解的持续。先前有研究表明，部分AML患者具有较高的抗mtg8抗体滴度。MTG8在正常成人组织中的表达要么无法检测到，要么只能微弱检测到。我们假设MTG8基因在t(8; 21) AML细胞中过表达可能作为肿瘤抗原，从而诱导免疫介导的MRD扩增抑制。我们能够使用健康供体的单核细胞来源树突状细胞诱导hla - a0201限制的细胞毒性t淋巴细胞（CTL）系对抗MTG8肽（MTG8b aa182-191）。T细胞受体（TCR） Vα17、TCRVβ14、tcrv β 15和TCR…更多的Jβ2.1，主要在这些CTL系中使用。我们的数据表明MTG8蛋白可能是ctl识别的肿瘤抗原之一，这可能有助于进一步研究长期缓解的t(8; 21) AML HLA-A0201患者的TCR分析。37岁男性慢性髓性白血病（CML）在异基因骨髓移植后255天发生血液学复发。患者接受供体淋巴细胞输注（DLI）两次，剂量为5 × 10 μ l /kg T细胞。他在DLI后14周达到完全细胞遗传学缓解（CCR），并保持CCR状态17个月。未观察到急性慢性移植物抗宿主病（GVHD）。自然杀伤（NK）细胞活性升高。此外，对TCR库的分析揭示了TCR Vβ和Jβ亚家族的T细胞寡克隆。这些观察结果为能够介导抗白血病活性而不引起GVHD的同种异体T细胞的克隆扩增提供了证据。少

项目成果

大久保亮子、吉田哲也、木村暢宏、他: "甲状腺機能低下症を伴ったSystemic Castleman病の1例"内科学会雑誌. 88(7). 1321-1323 (1999)

Ryoko Okubo、Tetsuya Yoshida、Nobuhiro Kimura 等：“与甲状腺功能减退相关的系统性 Castleman 病的病例”，日本内科学会杂志 88(7) 1321-1323 (1999)。

Nagano M, Kimura N, Ishii E, et al.: "Clonal Expansion of αβ-T Lymphocytes with Inverted JβBias in Familial Hemophagocytic Lymphohistiocytosis"Blood. 94(7). 2374-2382 (1999)

Nagano M、Kimura N、Ishii E 等人：“家族性噬血细胞性淋巴组织细胞增多症中具有反向 Jβ 偏差的 αβ-T 淋巴细胞的克隆扩增”，血液 94(7)。

Yoshida T, Kimura N et al: "CD56ィイD1+ィエD1CD7ィイD1+ィエD1 stem cell leukemia/lymphoma with D2-Jδ1 rearrangement"Internal Medicine. 38(7). 547-555 (1999)

Yoshida T、Kimura N 等人：“具有 D2-Jδ1 重排的 CD56D1+D1CD7D1+D1 干细胞白血病/淋巴瘤”Internal Medicine 38(7) (1999)。

Nagano M,Kimura N,Ishii E,et al: "Clonal Expansion of αβ-T Lymphocytes with Inverted Jβ Bias in Familial Hemophagosytic Lymphohistiocytosis."Blood. 94(7). 2374-2382 (1999)

Nagano M、Kimura N、Ishii E 等人：“家族性噬血性淋巴组织细胞增多症中具有反向 Jβ 偏差的 αβ-T 淋巴细胞的克隆扩增”。血液 94(7)。

Takimoto Y, Imanaka F, Sasaki N, Nanba K, Kimura N.: "γ/δ T-cell lymphomas presenting in the subcutaneous tissue and small intestine in a patient with capillary syndrome."Int. J. Hematology. 68(2). 183-191 (1998)

Takimoto Y、Imanaka F、Sasaki N、Nanba K、Kimura N.：“毛细血管综合征患者皮下组织和小肠中出现的 γ/δ T 细胞淋巴瘤。”Int。血液学 68(2)。 .183-191 (1998)