Miller C L, Hooton J W, Gillis S, Paetkau V
Department of Biochemistry, University of Alberta, Edmonton, Canada.
J Immunol. 1990 Feb 15;144(4):1331-7.
In addition to the regulation of B lymphocyte growth and differentiation, the cytokine IL-4 (BSF-1) exerts effects on T lymphocytes and other bone marrow-derived lineages. We show here that recombinant mouse IL-4 synergizes with low levels of IL-2 to increase the yield of cytotoxic activity in a primary MLR, and the proliferation of both cloned IL-2-dependent CTL lines and cells obtained from a primary MLR. IL-4 did not induce the proliferation of any of several cloned CTL cell lines on its own. It also did not replace IL-2 in stimulating the growth or reactivation of quiescent, antigen-dependent CTL clones. However, IL-4 was synergistic with IL-2 after reactivation of the quiescent cells with antigen plus IL-2. Enhancement by IL-4 of the IL-2-driven proliferation of an antigen-independent line was blocked by the addition of anti-IL-4 monoclonal antibody. Although incubation of the CTL clones with IL-4 or with IL-2 plus IL-4 induced a transient increase in the expression of the mRNA encoding the 55 kDa IL-2 receptor, no change in the number or affinity of IL-2 receptors because of IL-4 was detected. This suggests that IL-4 does not potentiate the IL-2 response by altering IL-2 receptor levels. Instead, we propose that the synergistic effect of IL-4 is mediated by a different signalling mechanism from that used by IL-2.
除了调节B淋巴细胞的生长和分化外,细胞因子白细胞介素-4(BSF-1)还对T淋巴细胞和其他骨髓来源的细胞谱系产生作用。我们在此表明,重组小鼠白细胞介素-4与低水平的白细胞介素-2协同作用,可提高初次混合淋巴细胞反应(MLR)中细胞毒性活性的产量,以及克隆的白细胞介素-2依赖性细胞毒性T淋巴细胞(CTL)系和从初次MLR获得的细胞的增殖。白细胞介素-4自身不会诱导几种克隆的CTL细胞系中的任何一种增殖。在刺激静止的、抗原依赖性CTL克隆的生长或再激活方面,它也不能替代白细胞介素-2。然而,在用抗原加白细胞介素-2使静止细胞再激活后,白细胞介素-4与白细胞介素-2具有协同作用。添加抗白细胞介素-4单克隆抗体可阻断白细胞介素-4对白细胞介素-2驱动的非抗原依赖性细胞系增殖的增强作用。尽管用白细胞介素-4或白细胞介素-2加白细胞介素-4孵育CTL克隆会导致编码55 kDa白细胞介素-2受体的mRNA表达短暂增加,但未检测到由于白细胞介素-4导致的白细胞介素-2受体数量或亲和力的变化。这表明白细胞介素-4不会通过改变白细胞介素-2受体水平来增强白细胞介素-2反应。相反,我们提出白细胞介素-4的协同作用是由一种与白细胞介素-2不同的信号传导机制介导的。