Gruss H J, Pinto A, Gloghini A, Wehnes E, Wright B, Boiani N, Aldinucci D, Gattei V, Zagonel V, Smith C A, Kadin M E, von Schilling C, Goodwin R G, Herrmann F, Carbone A
Department of Medical Oncology and Applied Molecular Biology, Robert-Rössle Cancer Center, Humboldt University Berlin, Germany.
Am J Pathol. 1996 Aug;149(2):469-81.
The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.
CD30配体(CD30L)是肿瘤坏死因子配体超家族的II型跨膜糖蛋白。最近对CD30L的克隆使得研究人员能够探索其功能和组织分布。例如,重组CD30L已被证明可共刺激T细胞,并可作为霍奇金病(HD)衍生细胞系的促有丝分裂原。CD30L的反受体,即CD30,是一种I型细胞因子受体,在活化的T细胞、霍奇金和里德-斯特恩伯格(H-RS)细胞以及间变性大细胞淋巴瘤细胞中高度表达。在本研究中,重组膜结合型和可溶性人CD30L有助于产生一种单克隆抗体(M80),该抗体可识别转染细胞和天然细胞上的膜结合型CD30L。利用该试剂,通过免疫染色和流式细胞术检测了一组培养的淋巴瘤衍生细胞系以及原发性正常、反应性和HD累及的淋巴组织中CD30L的表达。在反应性淋巴结和扁桃体中,一小部分淋巴细胞、组织细胞和粒细胞表达CD30L。在HD病变的旁观者细胞(即围绕H-RS细胞的T细胞和粒细胞)中,CD30L表达水平较高。固定的粒细胞与CD30+细胞系相互作用的能力表明,细胞表面展示的天然CD30L具有功能活性。此外,在所研究的所有HD组织的原发性H-RS细胞中均能检测到CD30L,尽管染色强度较低,无论H-RS细胞的组织学亚型和表型如何(即CD30+/CD40+与CD30-/CD40+)。除CD30-结节性淋巴细胞为主型外,所有HD亚型的H-RS细胞上均可见CD30和CD30L的共表达,这可能表明这一对分子在旁分泌和/或自分泌促有丝分裂细胞相互作用中的应用。因此,单克隆抗体M80可能是研究培养细胞系以及来自正常、反应性和恶性组织的原代细胞中CD30L表达的有用工具。