Akiba H, Atsuta M, Yagita H, Okumura K
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Biochem Biophys Res Commun. 1998 Oct 9;251(1):131-6. doi: 10.1006/bbrc.1998.9376.
OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor superfamily first identified as a rat T cell activation marker. In the present study, we identified the rat ligand for OX40 (OX40L) by molecular cloning. Rat OX40L cDNA was cloned from a HTLV-1-transformed rat T cell line by cross-hybridization with mouse OX40L cDNA. The predicted rat OX40L polypeptide is composed of 199 amino acids, showing 80.9 and 43.3% homology to mouse and human OX40L, respectively. Expression of rat OX40L mRNA was found in HTLV-1-transformed rat T cell lines. Expression of OX40L on the cell surface of these HTLV-1-transformed rat T cell lines was also demonstrated by flow cytometric analysis with a soluble fusion protein composed of the extracellular region of the Fc portion of human IgG (OX40-Ig). To explore the function of rat OX40L, we generated cDNA transfectants stably expressing rat OX40L. The rat OX40L transfectants exhibited a potent costimulatory activity for proliferation and IL-2 production of anti-CD3-stimulated rat T cells. These results indicated that rat OX40L can provide an efficient costimulation for rat T cells and that it may be involved in HTLV-1-associated pathologies in the rat system as has been suggested in the human system.
OX40（CD134）是肿瘤坏死因子（TNF）受体超家族的成员，最初被鉴定为大鼠T细胞活化标志物。在本研究中，我们通过分子克隆鉴定了OX40的大鼠配体（OX40L）。大鼠OX40L cDNA是通过与小鼠OX40L cDNA交叉杂交从HTLV-1转化的大鼠T细胞系中克隆得到的。预测的大鼠OX40L多肽由199个氨基酸组成，分别与小鼠和人OX40L具有80.9%和43.3%的同源性。在HTLV-1转化的大鼠T细胞系中发现了大鼠OX40L mRNA的表达。用由人IgG Fc部分的细胞外区域组成的可溶性融合蛋白（OX40-Ig）进行流式细胞术分析，也证实了这些HTLV-1转化的大鼠T细胞系细胞表面OX40L的表达。为了探索大鼠OX40L的功能，我们构建了稳定表达大鼠OX40L的cDNA转染子。大鼠OX40L转染子对抗CD3刺激的大鼠T细胞的增殖和IL-2产生表现出强大的共刺激活性。这些结果表明，大鼠OX40L可以为大鼠T细胞提供有效的共刺激，并且它可能如在人类系统中所提示的那样参与大鼠系统中与HTLV-1相关的病理过程。
