Wasik M A, Seldin D C, Butmarc J R, Gertz R, Marti R, Maslinski W, Kadin M E
Department of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Leuk Lymphoma. 1996 Sep;23(1-2):125-36. doi: 10.3109/10428199609054811.
Three clonally related T-cell lymphoma lines (PB-1, 2A, and 2B) were examined for expression of IL-2, IL-4, and their receptors. All three lines were derived from a single patient who had an atypical, progressive T-cell lymphoproliferative disorder involving primarily skin (Davis, T.H. et al. 1992, N. Engl. J. Med. 326:1115). The PB-1 cell line was obtained from a relatively early, clinically indolent stage of the cutaneous lymphoma, whereas the 2A and 2B lines were established from a late, aggressive stage of the lymphoma. Reverse-transcriptase PCR performed with primer pairs specific for IL-2 and IL-4 showed that no mRNA coding for these cytokines was present in any of the lines with the exception of IL-4 mRNA in the 2A line. No IL-4 protein, however, was found in any of the cell lines including 2A by immunocytochemical staining with anti-IL-4 mAb. Accordingly, no bioactive IL-4 was present in the supernatants of these lines. In contrast, all three T-cell lymphoma lines contained mRNA for IL-2R alpha, IL-2R beta, IL-4R and common gamma chain. Immunocytochemical analysis revealed that only the PB-1 line stained strongly with mAbs specific for IL-2R alpha, IL-2R beta, and IL-4R whereas the 2A and 2B lines showed only limited staining with these mAbs. In contrast to expression of IL-2R alpha and IL-4R primarily on the cell surface, IL-2R beta was localized mainly in the cell cytoplasm. Testing supernatants of the cell lines by ELISA for the presence of soluble alpha chain of the IL-2R (sIL-2R) has shown that only PB-1 secreted a large amount of sIL-2R, whereas the 2A and 2B lines secreted lesser amounts. Furthermore, the PB-1 cells expressed a relatively large number of IL-4R as determined by IL-4 binding studies using an IL-4-alkaline phosphatase fusion protein. The remaining two lines displayed only limited binding of IL-4. Addition of IL-2 and/or IL-4 to the culture medium did not modulate growth of PB-1 and the other two lines. These findings may indicate that at least some types of T-cell lymphoma evolve from cells which lose the capacity to synthesize T-cell autocrine growth factors such as IL-2 and IL-4, and show progressive loss of receptors for these cytokines.
检测了三个克隆相关的T细胞淋巴瘤细胞系（PB - 1、2A和2B）中白细胞介素 - 2（IL - 2）、白细胞介素 - 4（IL - 4）及其受体的表达情况。这三个细胞系均来源于一名患有主要累及皮肤的非典型、进行性T细胞淋巴增殖性疾病的患者（Davis, T.H.等人，1992年，《新英格兰医学杂志》326:1115）。PB - 1细胞系取自皮肤淋巴瘤相对早期、临床惰性阶段，而2A和2B细胞系则建立于淋巴瘤的晚期侵袭性阶段。用针对IL - 2和IL - 4的特异性引物对进行逆转录聚合酶链反应（RT - PCR），结果显示除2A细胞系中有IL - 4信使核糖核酸（mRNA）外，其他细胞系均不存在编码这些细胞因子的mRNA。然而，通过用抗IL - 4单克隆抗体（mAb）进行免疫细胞化学染色，在包括2A在内的任何细胞系中均未发现IL - 4蛋白。因此，这些细胞系的培养上清液中不存在生物活性IL - 4。相反，所有三个T细胞淋巴瘤细胞系均含有IL - 2受体α链（IL - 2Rα）、IL - 2受体β链（IL - 2Rβ）、IL - 4受体（IL - 4R）和共同γ链的mRNA。免疫细胞化学分析显示，只有PB - 1细胞系与针对IL - 2Rα、IL - 2Rβ和IL - 4R的mAb呈强染色，而2A和2B细胞系与这些mAb仅呈有限染色。与IL - 2Rα和IL - 4R主要表达在细胞表面不同，IL - 2Rβ主要定位于细胞质中。通过酶联免疫吸附测定（ELISA）检测细胞系培养上清液中是否存在IL - 2受体的可溶性α链（sIL - 2R），结果显示只有PB - 1分泌大量sIL - 2R，而2A和2B细胞系分泌量较少。此外，通过使用IL - 4 - 碱性磷酸酶融合蛋白进行IL - 4结合研究确定，PB - 1细胞表达相对大量的IL - 4R。其余两个细胞系仅显示有限的IL - 4结合。向培养基中添加IL - 2和/或IL - 4并未调节PB - 1和其他两个细胞系的生长。这些发现可能表明，至少某些类型的T细胞淋巴瘤是由失去合成诸如IL - 2和IL - 4等T细胞自分泌生长因子能力并逐渐丧失这些细胞因子受体的细胞演变而来。
