Gruss H J, DaSilva N, Hu Z B, Uphoff C C, Goodwin R G, Drexler H G
Immunex Research and Development Corporation, Seattle, WA.
Leukemia. 1994 Dec;8(12):2083-94.
The CD30 antigen was originally described as a specific surface marker for Hodgkin's lymphoma. Recent work established CD30 as a member of the tumor necrosis factor/nerve growth factor receptor superfamily whose ligand (CD30L) has also been cloned and expressed; CD30L is active as membrane-bound type II glycoprotein. Here, CD30L mRNA expression was studied in a panel of 102 continuous human leukemia-lymphoma cell lines and was found only in four Burkitt lymphoma, one Burkit-type acute lymphoblastic leukemia and one non-Hodgkin's lymphoma (NHL) cell line. The product of CD30L mRNA is expressed as a membrane protein on the surface of these malignant B-cell lines. Treatment of these cell lines with soluble CD27L, phorbol ester or staphylococcus aureus Cowan antigen resulted in the enhancement of cell surface CD30L protein expression. CD30L mRNA was not detected in normal unstimulated peripheral blood (PB) monocytes, monocyte-derived macrophages, or T-cells, but was detected in primary granulocytes; exposure to activating reagents induced and upregulated CD30L transcription in these different PB populations. While CD40 and CD30L surface protein expression on PB monocytes could be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level. Similarly, PB monocyte-derived macrophages and granulocytes remained negative for CD30 mRNA and protein expression, regardless of stimulation. Only activated T-cells expressed CD30 mRNA and surface protein. CD30L-transfected cells and cells constitutively expressing CD30L delivered a similar stimulus for proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line KARPAS-299. These data provide strong evidence for the involvement in growth regulation of recombinant and natural CD30L through its interaction with the CD30 receptor. Collectively, these data suggest that the CD30L-CD30 interaction has potent biological activity and might play a critical role in the immune response and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.
CD30抗原最初被描述为霍奇金淋巴瘤的一种特异性表面标志物。最近的研究确定CD30是肿瘤坏死因子/神经生长因子受体超家族的成员，其配体（CD30L）也已被克隆和表达；CD30L作为膜结合型II糖蛋白具有活性。在此，我们在一组102个人类白血病-淋巴瘤连续细胞系中研究了CD30L mRNA的表达，结果仅在4个伯基特淋巴瘤、1个伯基特型急性淋巴细胞白血病和1个非霍奇金淋巴瘤（NHL）细胞系中发现。CD30L mRNA的产物在这些恶性B细胞系的表面表达为膜蛋白。用可溶性CD27L、佛波酯或金黄色葡萄球菌考恩抗原处理这些细胞系，可导致细胞表面CD30L蛋白表达增强。在正常未受刺激的外周血（PB）单核细胞、单核细胞衍生的巨噬细胞或T细胞中未检测到CD30L mRNA，但在原代粒细胞中检测到；暴露于激活试剂可诱导并上调这些不同PB细胞群体中的CD30L转录。虽然用γ干扰素处理可增强或诱导PB单核细胞表面的CD40和CD30L蛋白表达，但这些细胞在mRNA和蛋白水平上的CD30均为阴性。同样，PB单核细胞衍生的巨噬细胞和粒细胞无论是否受到刺激，其CD30 mRNA和蛋白表达均为阴性。只有活化的T细胞表达CD30 mRNA和表面蛋白。CD30L转染细胞和组成性表达CD30L的细胞对CD30+霍奇金病（HD）衍生细胞系HDLM-2的增殖产生类似的刺激作用，但抑制CD30+间变性大细胞淋巴瘤细胞系KARPAS-299的增殖。这些数据为重组和天然CD30L通过与CD30受体相互作用参与生长调节提供了有力证据。总体而言，这些数据表明CD30L-CD30相互作用具有强大的生物学活性，可能在HD和某些NHL，特别是伯基特淋巴瘤的免疫反应和发病机制中起关键作用。
