Bowen M A, Lee R K, Miragliotta G, Nam S Y, Podack E R
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
J Immunol. 1996 Jan 15;156(2):442-9.
Murine CD30 cDNA predicts a protein of 498 amino acids with homology to the TNF receptor family of proteins characterized by repeated cysteine-rich motifs in the extracellular domain. Murine CD30, although homologous to human CD30, has a 90 amino acid gap in an extracellular region that appears to be duplicated in human CD30. Murine CD30 cDNA was shown to be functional through the production of a soluble murine Ig fusion protein (CD30-Ig) that was active in binding to cells that expressed CD30 ligand. CD30-Ig also served as an immunogen for the production of hamster anti-mouse CD30 mAbs, which recognized both CD30 expressed by murine lymphocytes and CD30 expressed by cells transfected with murine CD30 cDNA. CD30 mRNA is highly expressed in the thymus and in activated spleen cells, but not in other tissues tested. In anti-CD3-activated spleen cells, CD30 ligand is expressed primarily by CD4+ T cells, with peak expression at days 1 and 2, whereas CD30 is expressed primarily by CD8+ T cells, with peak expression on days 4 and 5. Stimulation of CD30 by plate-bound anti-CD30 directly signaled for IL-5 but not IFN-gamma production by CD30+ CTL lines. These studies demonstrate that CD30 directs cytokine secretion and suggest that CD30 signaling may be pivotal in the pattern of cytokine production by T cells.
小鼠CD30 cDNA预测的蛋白质由498个氨基酸组成,与肿瘤坏死因子受体家族的蛋白质具有同源性,其特征是细胞外结构域中有重复的富含半胱氨酸的基序。小鼠CD30与人CD30虽然同源,但在细胞外区域有一个90个氨基酸的缺口,而这个缺口在人CD30中似乎是重复的。通过产生可溶性小鼠Ig融合蛋白(CD30-Ig),小鼠CD30 cDNA被证明具有功能,该融合蛋白能与表达CD30配体的细胞结合。CD30-Ig还作为免疫原用于产生仓鼠抗小鼠CD30单克隆抗体,这些抗体能识别小鼠淋巴细胞表达的CD30以及用小鼠CD30 cDNA转染的细胞表达的CD30。CD30 mRNA在胸腺和活化的脾细胞中高度表达,但在其他检测的组织中不表达。在抗CD3活化的脾细胞中,CD30配体主要由CD4 + T细胞表达,在第1天和第2天表达达到峰值,而CD30主要由CD8 + T细胞表达,在第4天和第5天表达达到峰值。用固定在平板上的抗CD30刺激CD30直接诱导CD30 + CTL系产生IL-5,但不产生IFN-γ。这些研究表明,CD30指导细胞因子分泌,并提示CD30信号传导可能在T细胞产生细胞因子的模式中起关键作用。