Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL 4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell.
Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL 4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell.
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T 细胞的自分泌生长不依赖于白细胞介素 2：鉴定白细胞介素 4（IL 4、BSF-1）作为克隆的抗原特异性辅助 T 细胞的自分泌生长因子。
作者：
T. Kupper;M. Horowitz;F. Lee;R. Robb;P. Flood
白细胞介素4（IL 4），以前称为B细胞刺激因子1（BSF-1），最近被描述为T细胞的生长因子。IL 4在某些克隆的T辅助细胞的非IL 2依赖性生长中的作用尚不清楚。D10.G4.1（D10）是一种伴白蛋白特异性辅助T细胞，其已广泛用于T细胞活化的分析和作为检测IL 1的测定。以前，人们认为IL 1诱导D10细胞上IL 2受体的表达，从而允许D10响应内源性产生的IL 2而增殖。但是，我们不能在D10细胞或其上清中检测到IL-2的mRNA或蛋白，这是根据以下标准确定的：中和鼠IL-2体外活性的单克隆抗体不能阻断D10细胞的IL-1依赖性增殖，在活化的D10细胞条件培养基中不能检测到高亲和力IL-2受体与125 I标记的IL-2的竞争性结合;用IL 2的cDNA探针进行的北方印迹分析和S1核酸酶保护测定，在促进D10细胞自分泌生长的各种不同活化条件下均未检测到IL 2的mRNA。与此相反，活化的D10细胞产生IL 4 mRNA和蛋白质，如通过类似的标准判断的。HT-2细胞增殖实验表明，纯化的IL-4具有明显的TCGF活性.这种活性可被IL 4单克隆抗体（11B 11）完全阻断。11B 11抗体可完全阻断3D 3（一种克隆型特异性的抗T细胞受体单克隆抗体）和IL 1对D10细胞增殖的抑制作用。高纯度的IL 4单独不能诱导静息D10细胞的增殖;然而，等量的IL 4在重组IL 1的存在下诱导显著的D10增殖。因此，IL 1似乎使D10细胞对其自分泌生长信号作出反应。这些数据表明，IL 4作为D10细胞的自分泌T细胞生长因子，并且外源性IL 1是该生长信号转导所必需的。这可能代表了T辅助细胞的某些亚群的生长的更广泛适用的机制。
Interleukin 4 (IL 4), formerly known as B cell stimulatory factor 1 (BSF-1), has recently been described as a growth factor for T cells. The role of IL 4 in the putatively IL 2-independent growth of certain cloned T helper cells is unclear. D10.G4.1 (D10) is a conalbumin-specific helper T cell that has been employed extensively in the analysis of T cell activation and as an assay for the detection of IL 1. Previously, it was thought that IL 1 induced the expression of IL 2 receptors on D10 cells, thereby permitting D10 to proliferate in response to endogenously produced IL 2. However, we cannot detect IL 2 mRNA or protein in D10 cells or their supernatants as determined by the following criteria: monoclonal antibodies that neutralize the in vitro activity of murine IL 2 do not block the IL 1-dependent proliferation of D10 cells; no competitive binding for high-affinity IL 2 receptors with 125I-labeled IL 2 can be detected with medium conditioned by activated D10 cells; and Northern blot analysis and S1 nuclease protection assays, performed with cDNA probes for IL 2, do not detect mRNA for IL 2 under a variety of different activation conditions that foster autocrine growth of D10 cells. In contrast, activated D10 cells produce both IL 4 mRNA and protein as judged by similar criteria. Purified IL 4 has significant TCGF activity as measured by proliferation of HT-2 cells. This activity can be blocked completely by a monoclonal antibody to IL 4 (11B11). The proliferation of D10 cells in the presence of 3D3 (a clonotype-specific monoclonal anti-T cell receptor antibody) and IL 1 can be blocked completely by 11B11 antibody. Highly purified IL 4 alone cannot induce the proliferation of resting D10 cells; however, equivalent amounts of IL 4 in the presence of recombinant IL 1 induce significant D10 proliferation. Therefore, IL 1 appears to render D10 cells responsive to their autocrine growth signal. These data indicate that IL 4 serves as the autocrine T cell growth factor for D10 cells, and that exogenous IL 1 is required for the transduction of this growth signal. This may represent a more broadly applicable mechanism for the growth of certain subsets of T helper cells.