Cytokine and natural killing regulation of growth of a hairy cell leukemia-like cell line: the role of interferon-alpha and interleukin-2.
Cytokine and natural killing regulation of growth of a hairy cell leukemia-like cell line: the role of interferon-alpha and interleukin-2.
复制标题
毛细胞白血病样细胞系生长的细胞因子和自然杀伤调节：干扰素-α和白介素-2的作用。
DOI：
10.1097/00002371-199201000-00005
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Taylor,MW
中科院分区：
文献类型：
--
作者：
Reiter,Z;Ozes,ON;Blatt,LM;Taylor,MW
毛细胞白血病（HCL）是一种B淋巴细胞增生性疾病，其病理表现通常包括脾肿大和全血细胞减少。天然存在的和重组的干扰素（IFN），特别是[α]亚型，在HCL患者中显示出显著的抗肿瘤作用，在治疗的最初几个月内改善了血液学参数。在HCL患者中负责IFN-[alpha]有益作用的机制尚不清楚，但已提出了几种假设。最近，从诊断为毛细胞白血病的患者中建立了连续细胞系（Eskol），并显示具有白血病毛细胞的几种特性。在本研究中，我们研究了IFN-α和白细胞介素（IL-2）对Eskol细胞系的直接作用，以及淋巴因子对这些细胞的自然杀伤（NK）活性的调节。发现IFN-α对Eskol细胞具有直接的抗增殖作用。此外，发现Eskol细胞对NK细胞介导的细胞毒性（CMC）完全耐受，但对IFN-[α]引发的NK或淋巴因子激活的杀伤（LAK）细胞-CMC有些敏感。Eskol细胞对NK-CMC的抗性是由于对效应细胞的低结合能力。此外，发现IL-2与IFN一样，可以保护Eskol细胞免受活化的NK-CMC的影响。两种细胞因子均降低了Eskol细胞诱导NK细胞释放NK细胞毒性因子（NKCF）的能力，随后Eskol细胞和效应细胞之间形成缀合物。此外，放线菌酮治疗取消了对NK-CMC诱导的IFN-[α]或IL-2的保护作用。因此，似乎通过相同的机制介导了由两种细胞因子诱导的针对NK-CMC的保护作用。
Hairy cell leukemia (HCL) is a lymphoproliferative disorder of B-lymphocytes, with pathological manifestations usually including splenomegaly and pancytopenia. Naturally occurring and recombinant interferons (IFNs), specifically of the [alpha] subtype, have shown a significant anti-tumor effect in HCL patients, with improvement of hematologic parameters within the first few months of treatment. The mechanisms responsible for the beneficial action of IFN-[alpha] in HCL patients are unclear, but several hypotheses have been suggested. Recently, a continuous line of cells (Eskol) from a patient diagnosed with hairy cell leukemia was established and shown to have several properties of a leukemic hairy cell. In the present study, we investigated the direct effect of IFN-[alpha] and interleukin (IL-2) on the Eskol cell line, and lymphokine regulation of natural killing (NK) activity against these cells. It was found that IFN-[alpha] has a direct antiproliferative effect on Eskol cells. Furthermore, Eskol cells were found to be completely resistant to NK-cell mediated cytotoxicity (CMC) but were somewhat sensitive to either IFN-[alpha]-primed NK or lymphokine-activated killer (LAK) cells-CMC. The resistance of Eskol cells to NK-CMC is due to a low binding ability to effector cells. Moreover, it was found that like IFN, IL-2 can protect Eskol cells from activated NK-CMC. Both cytokines reduced the ability of Eskol cells to induce NK-cytotoxic factor (NKCF) release from NK cells following conjugate formation between Eskol cells and effector cells. Moreover, cycloheximide treatment abolished the protective effect against NK-CMC induced by IFN-[alpha] or by IL-2. Therefore, it seems that the protective effect against NK-CMC induced by both cytokines is mediated via the same mechanism.