T-CELL LYMPHOMA MODEL FOR THE ANALYSIS OF INTERLEUKIN 1-MEDIATED T-CELL ACTIVATION
T-CELL LYMPHOMA MODEL FOR THE ANALYSIS OF INTERLEUKIN 1-MEDIATED T-CELL ACTIVATION
复制标题
DOI：
10.1073/pnas.78.2.1133
复制
发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
MIZEL, SB
中科院分区：
文献类型：
--
作者：
GILLIS, S;MIZEL, SB
巨噬细胞衍生多肽IL-1(IL-1；以前称为淋巴细胞激活因子)可以绕过巨噬细胞在有丝分裂原诱导的小鼠T细胞白介素2(IL-2；以前称为T细胞生长因子)产生过程中对巨噬细胞的要求。以2例克隆性[小鼠]T细胞淋巴瘤为模型，研究了IL-1对IL-2产生的影响机制。使用的一个细胞系(LBRM-33 5A4)在有丝分裂原刺激下产生大量IL-2；第二个细胞系(LBRM-33 1A5)不能产生对有丝分裂原反应的IL-2。将纯化的IL-1加入到不产生IL-1的1A5细胞中，将它们转化为一种状态，在这种状态下，随后的丝裂原刺激会触发IL-2的产生。IL-1处理的1A5细胞产生的IL-2浓度与有丝分裂原刺激的5A4细胞产生的IL-2浓度相当(500-1000U/ml，约为传统小鼠有丝分裂原条件培养液中IL-2浓度的1000倍)。观察到短期暴露于IL-1就足以使1A5细胞转化为IL-2，并且IL-1可以被活的或固定的1A5细胞从培养上清液中主动吸收，从而提出了在响应的1A5细胞上存在IL-1受体的假设。IL-1可能通过使未成熟的T细胞亚群成熟到能够产生IL-2的程度来介导其对免疫反应的影响(促进胸腺细胞有丝分裂以及诱导抗体和细胞毒性T细胞反应)。随后在配体激活后释放IL-2，允许激活的T细胞克隆性扩增，介导特定的效应器功能。
The requirement for macrophages in mitogen-induced production of murine T cell interleukin 2 (IL-2; formerly referred to as T cell growth factor) can be circumvented by using the macrophage-derived peptide interleukin 1 (IL-1; formerly referred to as lymphocyte-activating factor). Using 2 cloned [mouse] T cell lymphomas, the mechanism through which IL-1 exerted its effect on IL-2 production was investigated. One cell line used (LBRM-33 5A4) produces large concentrations of IL-2 upon mitogen stimulation; the 2nd (LBRM-33 1A5) is incapable of producing IL-2 in response to mitogen. Addition of purified IL-1 to nonproducer 1A5 cells converted them to a state in which subsequent mitogen stimulation triggered production of IL-2. The concentration of IL-2 produced by IL-1-treated 1A5 cells was equivalent in magnitude to that generated by mitogen-stimulated 5A4 cells (500-1000 U/ml, or approximately 1000 times the concentration of IL-2 contained in conventional preparations of murine mitogen-conditioned medium). The observations that brief exposure to IL-1 was sufficient for 1A5 cell conversion to IL-2 production and that IL-1 could actively be absorbed from culture medium by live or fixed 1A5 cells led to the proposal of the existence of IL-1 receptors on responsive 1A5 cells. IL-1 probably mediates its effect on immune reactivity (enhancement of thymocyte mitogenesis and induction of antibody and cytotoxic T cell responses) by maturation of a subset of immature T cells to the point in which they are capable of IL-2 production. Subsequent release of IL-2 after ligand activation allows for clonal expansion of activated T cells which mediate particular effector functions.