Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells
Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells
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DOI：
10.1182/blood.v92.1.252.413k08_252_258
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发表时间：
1998-07-01
期刊：
影响因子：
20.3
通讯作者：
Burg, G
中科院分区：
文献类型：
--
作者：
Döbbeling, U;Dummer, R;Burg, G
在这项研究中，我们研究了白细胞介素-15（IL-15）在皮肤T细胞淋巴瘤（CTCL）细胞免疫生物学中的作用。使用细胞培养技术，逆转录-聚合酶链反应（RT-PCR）和免疫组化，我们发现，IL-15，IL-7一样，是Sezary细胞系SeAx的生长因子，这两种细胞因子延长了直接从Sezary综合征（SS）患者中分离的恶性T细胞的生存期。IL-15和IL-7都比IL-2更有效。其受体与IL-2、IL-7和IL-15的受体共享相同γ链的IL-4和IL-9不能维持CTCL细胞的生长，表明通过共同γ链（γ c）的信号传导不足以持续生长。IL-13和肿瘤坏死因子-α（TNF-α）没有影响。IL-7和IL-15也支持SeAx细胞在细胞凋亡诱导剂地塞米松和视黄酸存在下的生长。RT-PCR分析患者Sezary细胞和三种CTCL细胞系显示，所有这些细胞表达IL-15 mRNA，但只有少数（25%）产生IL-7 mRNA。SS和蕈样肉芽肿患者的皮肤活检样本的免疫组织化学分析显示，基底细胞层角质形成细胞和浸润淋巴细胞中的IL-15的免疫反应性。我们得出结论，IL-15是CTCL衍生的细胞系或短期培养的Sezary细胞的生长或活力因子。IL-15 mRNA可在Sezary综合征外周血单个核细胞中检测到，IL-15蛋白可在CTCL患者的皮肤切片中检测到，这一发现表明IL-15在CTCL的生物学中起重要作用。(C)1998年，美国血液学会。
In this study we investigated the role of interleukin-15 (IL-15) in the immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the Sezary cell line SeAx and that both cytokines prolonged the survival of malignant T cells directly isolated from Sezary syndrome (SS) patients. Both IL-15 and IL-7 were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma chain with the receptors of IL-2 IL-7, and IL-15, did not sustain the growth of CTCL cells, indicating that signaling through the common gamma chain (gamma c) is not sufficient for continuous growth. IL-13 and tumor necrosis factor-alpha (TNF-alpha) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in the presence of the apoptosis inducing agents dexamethasone and retinoic acid. The analysis of patient Sezary cells and three CTCL cell lines by RT-PCR showed that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7 mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis fungoides patients showed immunoreactivity for IL-15 in basal cell layer keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a growth or viability factor for CTCL-derived cell lines or shortly cultivated Sezary cells. The findings that IL-15 mRNA can be detected in Sezary syndrome peripheral blood mononuclear calls and that the IL-15 protein is detected in skin sections from CTCL patients suggest that IL-15 plays an important role in the biology of CTCL. (C) 1998 by The American Society of Hematology.