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人T细胞白血病病毒I型感染的免疫人T细胞克隆中的转化及细胞病变效应

Transformation and cytopathogenic effect in an immune human T-cell clone infected by HTLV-I.

作者信息

Mitsuya H, Guo H G, Megson M, Trainor C, Reitz M S, Broder S

出版信息

Science. 1984 Mar 23;223(4642):1293-6. doi: 10.1126/science.6322299.

Abstract

Human T-cell leukemia-lymphoma virus (HTLV) is a human C-type retrovirus that can transform T lymphocytes in vitro and is associated with certain T-cell neoplasms. Recent data suggest that, in the United States, patients with acquired immunodeficiency syndrome (AIDS), homosexual men with lymphadenopathy, and hemophiliacs have had significant exposure rates to HTLV, whereas matched and unmatched control American subjects have rarely been exposed to this agent. In the present experiments, T cells specifically reactive against HTLV were propagated from a patient whose HTLV-bearing lymphoma was in remission. The T cells were cloned in the presence of the virus and an HTLV-specific cytotoxic T-cell clone was isolated. This clone was infected and transformed by the virus, with one copy of an HTLV-I provirus being integrated into the genome. This T-cell clone did not exhibit the normal dependence on T-cell growth factor (interleukin-2) and proliferated spontaneously in vitro. Exposure of the clone to HTLV-bearing, autologous tumor cells specifically inhibited its proliferation and resulted in its death. These results may have implications for HTLV-associated inhibition of T-cell responses.

摘要

人类T细胞白血病-淋巴瘤病毒(HTLV)是一种人类C型逆转录病毒,它能够在体外转化T淋巴细胞,并与某些T细胞肿瘤相关。最近的数据表明,在美国,获得性免疫缺陷综合征(AIDS)患者、患有淋巴结病的同性恋男性以及血友病患者感染HTLV的比例相当高,而与之匹配及不匹配的美国对照受试者很少接触到这种病原体。在当前的实验中,从一名HTLV携带的淋巴瘤处于缓解期的患者体内培养出了对HTLV具有特异性反应的T细胞。这些T细胞在病毒存在的情况下进行克隆,并分离出了一个HTLV特异性细胞毒性T细胞克隆。该克隆被病毒感染并转化,一个HTLV-I前病毒拷贝整合到了基因组中。这个T细胞克隆对T细胞生长因子(白细胞介素-2)没有正常的依赖性,并且在体外能够自发增殖。将该克隆暴露于携带HTLV的自体肿瘤细胞中会特异性抑制其增殖并导致其死亡。这些结果可能对HTLV相关的T细胞反应抑制具有启示意义。

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