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TCGF(白细胞介素2)受体诱导因子。II.成人T细胞白血病衍生因子(ADF)对人嗜T淋巴细胞病毒I型(HTLV-I)阳性T细胞系组成性白细胞介素2受体表达的可能作用。

TCGF(IL 2)-receptor inducing factor(s). II. Possible role of ATL-derived factor (ADF) on constitutive IL 2 receptor expression of HTLV-I(+) T cell lines.

作者信息

Okada M, Maeda M, Tagaya Y, Taniguchi Y, Teshigawara K, Yoshiki T, Diamantstein T, Smith K A, Uchiyama T, Honjo T

出版信息

J Immunol. 1985 Dec;135(6):3995-4003.

PMID:2999237
Abstract

Interleukin 2 (IL 2) receptor (IL 2-R) is constitutively expressed on T cell lines established from the patients with adult T cell leukemia (ATL), which is a human T cell leukemia lymphoma virus (HTLV-1)(+) T4(+)-leukemia endemic in Japan, the United States, and other countries. Many of these cell lines continuously produce an acidic lymphokine, ATL-derived factor (ADF), which preferentially induces the synthesis and expression of IL 2-R on a sensitive HTLV-1(-) non-T cell line (YT). The induced IL 2-R was characterized by the binding of 125I-IL 2 and flow cytometry by using fluoresceinated anti-human IL 2-R monoclonal antibodies (anti-Tac). Scatchard analysis with 125I-IL 2 showed ADF induced high-affinity receptor sites on YT cells. To test the possibility that ADF produced by HTLV-1(+) T cells is involved in the abnormal expression of IL 2-R, we studied the effect of ADF on an HTLV-1(+) IL 2-dependent T cell line (ED) in which the beta-chain gene of the T cell antigen receptor (T beta) was rearranged. Unlike IL 2-independent HTLV-1(+) cell lines that constitutively expressed Il 2-R, the IL 2-R expression on ED cells declined in the absence of crude IL 2 or recombinant IL 2. When either ADF or recombinant IL 2 was added to the culture of ED cells, there was a dose-dependent enhancement of IL 2-R expression in 24 hr. ADF and IL 2 showed a synergism in the IL 2-R induction, and both factors were needed to induce the maximal receptor expression in these T cells. The lack of IL 2 production by ADF-treated YT, as well as ED cell line suggested IL 2 may not be involved in the IL 2-R induction by ADF. Northern blot hybridization with human IL 2-R cDNA probe showed the increase of IL 2-R mRNA in YT cells after ADF-treatment. ADF also enhanced IL 2-R expression of a rat T cell line transformed by HTLV-1(TARS-1), as demonstrated with anti-rat IL 2 receptor monoclonal antibodies (ART-18). An ADF-like IL 2-R-inducing factor was also detected in the conditioned medium of two HTLV-1(+) rat T cell lines (TARL-2 and TART-1), which constitutively expressed a higher number of Il 2-R than TARS-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

白细胞介素2(IL-2)受体(IL-2-R)在从成人T细胞白血病(ATL)患者中建立的T细胞系上组成性表达,成人T细胞白血病是一种在日本、美国和其他国家流行的人类T细胞白血病淋巴瘤病毒(HTLV-1)(+)T4(+)白血病。这些细胞系中的许多持续产生一种酸性淋巴因子,即ATL衍生因子(ADF),它优先诱导敏感的HTLV-1(-)非T细胞系(YT)上IL-2-R的合成和表达。通过使用荧光素化抗人IL-2-R单克隆抗体(抗-Tac),以125I-IL-2的结合和流式细胞术对诱导的IL-2-R进行了表征。用125I-IL-2进行的Scatchard分析表明,ADF在YT细胞上诱导了高亲和力受体位点。为了测试HTLV-1(+)T细胞产生的ADF是否参与IL-2-R的异常表达,我们研究了ADF对一种HTLV-1(+)IL-2依赖性T细胞系(ED)的影响,该细胞系中T细胞抗原受体(Tβ)的β链基因发生了重排。与组成性表达IL-2-R的IL-2非依赖性HTLV-1(+)细胞系不同,在没有粗制IL-2或重组IL-2的情况下,ED细胞上的IL-2-R表达下降。当将ADF或重组IL-2添加到ED细胞培养物中时,24小时内IL-2-R表达呈剂量依赖性增强。ADF和IL-2在IL-2-R诱导中表现出协同作用,并且两种因子都需要诱导这些T细胞中最大的受体表达。ADF处理的YT以及ED细胞系缺乏IL-2产生,这表明IL-2可能不参与ADF诱导IL-2-R。用人IL-2-R cDNA探针进行的Northern印迹杂交显示,ADF处理后YT细胞中IL-2-R mRNA增加。如用抗大鼠IL-2受体单克隆抗体(ART-18)所证实的,ADF还增强了由HTLV-1转化的大鼠T细胞系(TARS-1)的IL-2-R表达。在两种HTLV-1(+)大鼠T细胞系(TARL-2和TART-1)的条件培养基中也检测到了一种类似ADF的IL-2-R诱导因子,这两种细胞系组成性表达的IL-2-R数量比TARS-1细胞多。(摘要截短于400字)

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