Haasch Deanna, Chen Yung-Wu, Reilly Regina M, Chiou X Grace, Koterski Sandra, Smith Morey L, Kroeger Paul, McWeeny Kerri, Halbert Donald N, Mollison Karl W, Djuric Stevan W, Trevillyan James M
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
Cell Immunol. 2002 May-Jun;217(1-2):78-86. doi: 10.1016/s0008-8749(02)00506-3.
In a search for novel early T cell activation transcripts, we identified expressed sequence tags (ESTs) more abundantly expressed in normal human CD4(+) T lymphocytes fully activated by a 5 h exposure to CD3 plus CD28 mAbs, compared to the same cells stimulated with either CD3 mAb or CD28 mAb alone. An EST was identified that hybridized with a 1.7 kb transcript expressed in activated T cells but was undetectable by Northern blot analysis in resting T cells or other normal tissues. The T cell transcript was maximally induced within 6 h and remained elevated for at least 47 h. Induction of the transcript was blocked by cyclosporin A, FK506, and dexamethasone but not by rapamycin. The transcript was polyadenylated but lacked an open reading. A BLAST search of the NCBI database revealed that the transcript shared identity with the recently reported human BIC proto-oncogene that encodes a noncoding mRNA (W. Tam, Gene 274 (2001) 157). Our data demonstrate that transcriptional activation of the BIC proto-oncogene is an early and sustained T cell activation event and suggest an important role for noncoding mRNA in T cell function.
在寻找新型早期T细胞激活转录本的过程中，我们鉴定出了一些表达序列标签（ESTs），与单独用CD3单克隆抗体或CD28单克隆抗体刺激的相同细胞相比，这些ESTs在经5小时暴露于CD3加CD28单克隆抗体而完全激活的正常人CD4(+) T淋巴细胞中表达更为丰富。鉴定出一个EST，它与激活的T细胞中表达的1.7 kb转录本杂交，但在静息T细胞或其他正常组织中通过Northern印迹分析无法检测到。T细胞转录本在6小时内被最大程度地诱导，并至少持续升高47小时。转录本的诱导被环孢菌素A、FK506和地塞米松阻断，但不被雷帕霉素阻断。该转录本进行了多聚腺苷酸化，但缺乏开放阅读框。对NCBI数据库进行BLAST搜索显示，该转录本与最近报道的编码非编码mRNA的人类BIC原癌基因具有同一性（W. Tam，《基因》274 (2001) 157）。我们的数据表明，BIC原癌基因的转录激活是一个早期且持续的T细胞激活事件，并提示非编码mRNA在T细胞功能中具有重要作用。
