Hsu S M, Lin J, Xie S S, Hsu P L, Rich S
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.
Hum Pathol. 1993 Mar;24(3):249-55. doi: 10.1016/0046-8177(93)90034-e.
The depressed cellular immunity observed in patients with Hodgkin's disease (HD) has been attributed to production of transforming growth factor (TGF)-beta or TGF-beta-like substances by Hodgkin's Reed-Sternberg (H-RS) cells. The TGF-beta produced by L-428 cells (an H-RS cell line) is a 130-kd molecular weight glycoprotein that apparently differs from the TGF-beta (molecular weight, 25 kd) produced by most lymphoid and hematopoietic cells. Among several distinct types of TGF-beta that have been purified, only TGF-beta 1 and TGF-beta 2 have thus far been identified in hematopoietic cells. By using monoclonal antibodies (1D11 and 3C7) and oligonucleotide probes specific for TGF-beta 1 and TGF-beta 2, were confirmed that a cultured H-RS cell line, KM-H2, can produce both TGF-beta types, whereas another line, HDLM-1, produces only TGF-beta 1. Despite the abundance of mRNA in both of these cells, only small amounts of TGF-beta activity were detected, probably because of rapid degradation of TGF-beta 1 mRNA by specific nuclease. No degraded TGF-beta 2 RNA products were observed in KM-H2 cells. The TGF-beta produced by both types of H-RS cells had a molecular weight of approximately 25 kd. In tissues expression of TGF-beta was observed in a small portion (30%) of H-RS cells in 16 of 20 cases examined. A large number of small to medium-sized lymphoid cells (T lymphocytes) in tissues involved by HD also were positive for TGF-beta. These results indicate that there is functional heterogeneity among H-RS cells, and that H-RS cells are not the only source of TGF-beta in tissues involved by HD. Hodgkin's Reed-Sternberg cells are known to secrete several other cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha. These cytokines could be responsible for the increased number of T lymphocytes in tissues involved by HD. Furthermore, T lymphocytes can respond to IL-1 and IL-6 secreted by H-RS cells by increasing their production of TGF-beta. Abundant expression of TGF-beta by T lymphocytes was not observed in lymphoid tissues other than those involved by HD.
霍奇金淋巴瘤（HD）患者中观察到的细胞免疫抑制被归因于霍奇金-里德-斯腾伯格（H-RS）细胞产生转化生长因子（TGF）-β或TGF-β样物质。L-428细胞（一种H-RS细胞系）产生的TGF-β是一种分子量为130kd的糖蛋白，显然不同于大多数淋巴细胞和造血细胞产生的TGF-β（分子量25kd）。在已纯化的几种不同类型的TGF-β中，迄今为止在造血细胞中仅鉴定出TGF-β1和TGF-β2。通过使用针对TGF-β1和TGF-β2的单克隆抗体（1D11和3C7）和寡核苷酸探针，证实培养的H-RS细胞系KM-H2可产生这两种类型的TGF-β，而另一个细胞系HDLM-1仅产生TGF-β1。尽管这两种细胞中都有丰富的mRNA，但仅检测到少量的TGF-β活性，这可能是由于特异性核酸酶对TGF-β1 mRNA的快速降解所致。在KM-H2细胞中未观察到TGF-β2 RNA降解产物。两种类型的H-RS细胞产生的TGF-β分子量约为25kd。在所检查的20例病例中的16例中，在一小部分（30%）的H-RS细胞中观察到TGF-β的组织表达。HD累及组织中的大量中小淋巴细胞（T淋巴细胞）TGF-β也呈阳性。这些结果表明H-RS细胞之间存在功能异质性，并且H-RS细胞不是HD累及组织中TGF-β的唯一来源。已知霍奇金-里德-斯腾伯格细胞可分泌几种其他细胞因子，包括白细胞介素（IL）-1、IL-6和肿瘤坏死因子-α。这些细胞因子可能是HD累及组织中T淋巴细胞数量增加的原因。此外，T淋巴细胞可通过增加其TGF-β的产生来响应H-RS细胞分泌的IL-1和IL-6。除HD累及的淋巴组织外，在其他淋巴组织中未观察到T淋巴细胞大量表达TGF-β。
