ILA, THE HUMAN 4-1BB HOMOLOG, IS INDUCIBLE IN LYMPHOID AND OTHER CELL LINEAGES
ILA, THE HUMAN 4-1BB HOMOLOG, IS INDUCIBLE IN LYMPHOID AND OTHER CELL LINEAGES
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DOI：
10.1182/blood.v85.4.1043.bloodjournal8541043
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发表时间：
1995-02-15
期刊：
影响因子：
20.3
通讯作者：
LOTZ, M
中科院分区：
文献类型：
--
作者：
SCHWARZ, H;VALBRACHT, J;LOTZ, M
我们最近发现了一种由淋巴细胞激活（ILA）诱导的基因。全长 1.4 kb cDNA 的序列将 ILA 描述为神经生长因子/肿瘤坏死因子 (NGF/TNF) 受体家族的新成员以及鼠 T 细胞特异性受体 4-1BB 的人类同源物。本研究表明，来自激活而非静息的人外周血 T 淋巴细胞的多聚 A(+) RNA 中存在 4.4、4.0 和 1.8 kb 处的 ILA mRNA 亚型。使用逆转录酶聚合酶链反应 (RT-PCR) 测定来研究 ILA 表达的组织分布和调节。该基因在 T 淋巴细胞中由植物血凝素 (PHA)、佛波醇肉豆蔻酸酯 (PMA) 和 CD3 抗体诱导，在 B 淋巴细胞中由 PMA 和细胞表面 Ig 抗体诱导，在血液单核细胞中由白细胞介素 1 β (IL-1 β)、脂多糖 (LPS) 和 PMA 诱导。在 T 淋巴细胞中，刺激后 1.5 小时可检测到 ILA mRNA，在 8 小时时达到最高水平，并在 48 小时时降至背景水平。 ILA mRNA 的诱导需要蛋白质合成，主要是由于转录增加。放线菌素 D 在 30 分钟内将活化淋巴细胞中的 ILA mRNA 水平降低 50%，表明该 mRNA 的半衰期相对较短。对非淋巴细胞的分析表明，在静息细胞中检测不到 ILA mRNA。然而，与小鼠 4-1BB 基因的淋巴特异性表达相反，在用 IL-1 β 刺激后，在非淋巴细胞（包括上皮细胞和肝癌细胞）中检测到了 ILA。在几种脑源性细胞系中未检测到 ILA。体外翻译证明，ILA cDNA 编码 30 kD 蛋白质，并且该蛋白质可通过针对 ILA 肽或谷胱甘肽-S-转移酶融合蛋白产生的抗血清进行免疫沉淀。流式细胞术显示 ILA 蛋白在活化的 T 或 B 淋巴细胞亚群上表达。总之，ILA 的激活依赖性表达不仅存在于 T 淋巴细胞中，而且还存在于 B 淋巴细胞、单核细胞和多种非淋巴细胞类型中。 (C) 1995 年，美国血液学会。
We recently identified a gene that is induced by lymphocyte activation (ILA). The sequence of the full-length 1.4-kb cDNA characterized ILA as a new member of the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor family and the human homologue of the murine T-cell-specific receptor 4-1BB. The present study demonstrates ILA mRNA isoforms at 4.4, 4.0, and 1.8 kb in poly-A(+) RNA from activated, but not from resting human peripheral blood T lymphocytes. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to study tissue distribution and regulation of ILA expression. The gene was induced in T lymphocytes by phytohemagglutinin (PHA), phorbol myristate acetate (PMA), and antibody to CD3, in B lymphocytes by PMA and antibodies to cell surface Ig, and in blood monocytes by interleukin-1 beta (IL-1 beta), lipopolysaccharide (LPS), and PMA. In T lymphocytes, ILA mRNA was detectable 1.5 hours after stimulation, reached maximal levels at 8 hours, and declined to background levels by 48 hours. Induction of ILA mRNA required protein synthesis and was primarily due to increased transcription. Actinomycin D reduced ILA mRNA levels in activated lymphocytes 50% within 30 minutes, demonstrating a relatively short half-life of this mRNA, Analysis of nonlymphoid cells showed that ILA mRNA was not detectable in resting cells. However, in contrast to the lymphoid-specific expression of the murine 4-1BB gene, ILA was detected in nonlymphoid cells, including epithelial and hepatoma cells after stimulation with IL-1 beta. ILA was not detectable in several brain derived cell lines. The ILA cDNA encodes a 30-kD protein as demonstrated by in vitro translation, and this protein is immunoprecipitated by antisera that were raised against ILA peptides or a glutathione-S-transferase fusion protein. Flow cytometry showed expression of ILA protein on a subset of activated T or B lymphocytes. In conclusion, activation-dependent expression of ILA is found not only in T lymphocytes, but also in B lymphocytes, monocytes, and diverse nonlymphoid cell types. (C) 1995 by The American Society of Hematology.