Analysis of lymphomagenesis of NK lymphoma based on Epstein-Barr virus.

基于 Epstein-Barr 病毒的 NK 淋巴瘤发生机制分析。

• 批准号: 11671022
• 负责人: KAGAMI Yoshitoyo
• 金额: $ 2.11万
• 依托单位: Aichi cancer center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671022/
• 关键词: cytotoxic T-cell; follicular dendritic cell; lymphoma cell line; NK; T cell lymphoma; Epstein-Barr virus; 細胞傷害性T細胞

1. Clinico-pathological analysis of nodal T/NK cell lymphomas.We characterized 227 cases of nodal T/NK cell lymphomas and established cytotoxic molecule positive lymphoma. Among them, we found cytotoxic molecule (+)EBV(+) lymphoma cases which were newly categorized as cytotoxic large T-cell lymphoma.2. Characterization of NK/T cell lymphoma derived cell line HANK1A sub-clone which proliferated in the serum-free media was selected from the NK/T cell lymphoma derived cell line HANK1. Those cells proliferated only in the high cell concentration, and died in the presence of anti-CD56 or anti-CD7 monoclonal antibody.However, in the presence of human plasma, this sub-clone showed the resistance to the growth inhibition of anti-CD56 or anti-CD7 monoclonal antibody. Because fetal calf serum had adverse effect on the growth of HANK1, growth promoting activity of human plasma suggested the relevance to the poor prognosis of NK/T cell lymphoma.3. Induction of cytotoxic T-cell clone against NK/T cell lymphomaThe DNA typing of HANK1 showed HLA-A (0207, 2402) which is popular in Japanese. We are selecting cytotoxic T-cell clones against HLA-matched healthyvolunteers' B-cells which are immortalized by EBV.4. Reactivation mechanism of EBV in lymph nodesFrom the analysis of the association of EBV to nodal T/NK cell lymphomas, we found high rate of clonal infection in angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). As follicular dendritic cells (FDC) are abundant in AILD, cells in the lymph nodes of EBV-seropositive AILD patients were co-cultured with FDC derived cell line. We acquired EBV infected B cells whose growth was dependent on FDC derived cell line. Further studies about the roles of FDC in the reactivation of EBV are necessary.

1.结节T/NK细胞淋巴瘤的临床病理分析我们对227例结节T/NK细胞淋巴瘤进行了特征分析，并建立了细胞毒分子阳性的淋巴瘤。其中，我们发现了细胞毒性分子(+)EBV(+)淋巴瘤病例，新分类为细胞毒性大T细胞淋巴瘤。NK/T细胞淋巴瘤来源细胞系HANK1a亚克隆在无血清培养条件下增殖的研究这些细胞只有在高浓度的细胞中才能增殖，在抗CD56或抗CD7的单抗存在下死亡，但在人血浆存在下，该亚克隆对抗CD56或抗CD7的单抗的生长抑制表现出抵抗。由于胎牛血清对HANK1细胞的生长有不良影响，提示人血浆促生长活性与NK/T细胞淋巴瘤预后不良有关。诱导抗NK/T细胞淋巴瘤的细胞毒性T细胞克隆HANK1的DNA分型为在日本流行的人类白细胞抗原A(0207,2402)。我们正在选择细胞毒性T细胞克隆来对抗人类白细胞抗原相合的健康志愿者的B细胞，这些B细胞被EBV永生化。EBV在淋巴结中的再激活机制通过分析EBV与结节性T/NK细胞淋巴瘤的关系，我们发现在血管免疫母细胞淋巴结病伴蛋白异常血症(AILD)中，克隆性感染率很高。由于滤泡树突状细胞(FDC)在AILD中含量丰富，将EBV阳性的AILD患者的淋巴结细胞与FDC来源的细胞系进行共培养。我们获得了EBV感染的B细胞，其生长依赖于FDC来源的细胞系。有必要进一步研究FDC在EBV再激活中的作用。

项目成果

Kagami Y: "Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular dendritic cell-like cell line HK."Leukemia. 15. 148-156 (2001)

Kagami Y：“建立依赖于滤泡树突状细胞样细胞系 HK 的滤泡淋巴瘤细胞系 (FLK-1)。”白血病。

Kagami Y.: "Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular dendritic cell-like cell line HK."Leukemia. 15. 148-156 (2001)

Kagami Y.：“建立依赖于滤泡树突状细胞样细胞系 HK 的滤泡淋巴瘤细胞系 (FLK-1)。”白血病。

Kagami Y: "Cytotoxic large T-cell lymphoma with fulminant clinical course, CD8+ and CD5 6-phenotype, and its relation to Epstein-Barr virus : a report of two cases."Int J Hematol. 70. 105-111 (1999)

Kagami Y：“具有暴发性临床过程的细胞毒性大 T 细胞淋巴瘤、CD8 和 CD5 6 表型及其与 Epstein-Barr 病毒的关系：两个病例的报告。”Int J Hematol。