INFECTION OF HTLV-1-SPECIFIC IMMUNE T-CELL CLONES BY HTLV-I

HTLV-I 对 HTLV-1 特异性免疫 T 细胞克隆的感染

• 批准号: 3963326
• 负责人: H MITSUYA
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963326
• 关键词: cell growth regulation; cell transformation; clone cells; helper T lymphocyte; human T cell leukemia; human T cell lymphotropic virus type 1; human tissue; interleukin 2; leukocyte activation /transformation; neoplasm /cancer immunology; oncogenic virus; provirus; suppressor T lymphocyte; transforming virus; viral leukemia; viral leukemogenesis; virus infection mechanism

Human T-lymphotropic virus-I (HTLV-I)-specific T-cell lines were established and cloned. An OKT8+ cytotoxic clone (K5) was specifically reactive against HTLV-I-bearing autologous tumor cells, and it retained a normal dependence on interluekin 2 (IL-2). We observed multiple proviral integration sites in K5 cells (i.e., there was no dominant proviral integration site), suggesting that the number of integration sites which, when occupied, result in T-cell transformation is finite. An OKT4+ HTLV-I-infected clone (R2) mounted a specific proliferative response to HTLV-I; however, its IL-2-independent proliferation increased with time and the antigen-specificity was eventually lost. All HTLV-I-infected clones tested including another OKT8+ transformed cytotoxic clone (K7) which had lost its reactivity against HTLV-I, expressed T-cell receptor B chain (TCR-B) messenger RNA at comparable levels. Two clones (K5 and K7) had the same rearrangement of the TCR-B gene, suggesting that they have the same clonal origin, even though they exhibited different functional properties following HTLV-I infection. These data indicate that HTLV-I-specific immune T-cell clones with a range of functions can be infected with HTLV-I, retain their immune reactivity for variable periods of time in culture, and lose it, although in some cases no alteration in function following HTLV-I infection can be detected. In addition, the data suggest that different consequences can take place in the same clone depending on the pattern of retroviral infection.

人嗜T淋巴细胞病毒-I（HTLV-I）特异性T细胞系是 建立和克隆。 OKT 8+细胞毒性克隆（K5）特异性地被 对携带HTLV-I的自体肿瘤细胞具有反应性，并且它保留了 正常依赖白细胞介素2（IL-2）。 我们观察到多个前病毒 K5细胞中的整合位点（即，没有显性前病毒 整合位点），表明整合位点的数量， 当被占用时，导致T细胞转化是有限的。 OKT 4 + HTLV-I感染的克隆（R2）对HTLV-I产生特异性增殖反应， 然而，其IL-2非依赖性增殖随着时间的推移而增加， 抗原特异性最终丧失。 所有HTLV-I感染的克隆 测试包括另一个OKT 8+转化的细胞毒性克隆（K7）， 失去对HTLV-1的反应性，表达T细胞受体B链 （TCR-B）信使RNA在相当的水平。 两个克隆（K5和K7）具有 TCR-B基因的相同重排，表明它们具有相同的 克隆起源，即使它们表现出不同的功能特性， HTLV-I感染后。 这些数据表明，HTLV-I特异性免疫T细胞克隆具有一定的 的功能可以感染HTLV-I，保留其免疫反应性 在文化中的可变时间段，并失去它，虽然在一些 HTLV-I感染后功能无改变的病例， 检测到 此外，数据表明，不同的后果可以 发生在同一个克隆中，这取决于逆转录病毒的模式， 感染