Gootenberg J E, Ruscetti F W, Mier J W, Gazdar A, Gallo R C
J Exp Med. 1981 Nov 1;154(5):1403-18. doi: 10.1084/jem.154.5.1403.
Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, "autostimulation" may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.
人们发现,源自皮肤T细胞淋巴瘤白血病(CTCL)患者的三种成熟T细胞系是T细胞生长因子(L-TCGF)的组成型生产者。这些是首次报道的组成型产生TCGF的人类细胞系。在维持细胞活力的条件下,使用酸性甘氨酸缓冲液也可从这些细胞表面洗脱具有生物活性的TCGF,亚细胞分级分离显示几乎所有的TCGF活性都与质膜相关。源自其他疾病的30多种其他人类造血细胞系即使在诱导后也无法产生TCGF,其酸性洗脱液不含TCGF活性。CTCL细胞系的L-TCGF与从正常白细胞获得的TCGF(N-TCGF)具有相同的生物活性,即只有在细胞先前被抗原或凝集素激活后,它们才能支持正常T细胞的长期生长。L-TCGF和N-TCGF均提高了不依赖TCGF和依赖TCGF的CTCL细胞系的增殖速率。释放TCGF的相同三种不依赖因子的细胞系以细胞浓度、时间和温度依赖性方式吸附TCGF。由于CTCL细胞系产生TCGF、吸附TCGF,并响应TCGF或相关分子而提高其增殖速率,因此有人认为这种内源性产生的因子在维持这些细胞在培养中作为独立于外源性TCGF的永久生长细胞系的异常增殖中起作用。然而,这并不意味着这是肿瘤转化的一个基本方面。由于在没有持续添加TCGF的情况下培养这些细胞系是不寻常的,“自刺激”可能是有时与肿瘤细胞相关的许多不寻常的变异表型特性之一,这赋予它们在体外生长的选择性优势。