Miethke T, Schmidberger R, Heeg K, Gillis S, Wagner H
Department of Medical Microbiology and Immunology, University of Ulm, FRG.
Eur J Immunol. 1988 May;18(5):767-72. doi: 10.1002/eji.1830180517.
To analyze the role of interleukin 4 (IL4, BSF-1) during primary activation of resting (high-density) murine CD8 T cells, a model system was used which bypasses antigen-presenting cells by the use of anti-T3 monoclonal antibodies immobilized on Sepharose beads. In high, but not in low cell density cultures, IL4 alone induced cell growth. In low cell density cultures, further to T3 cross-linking a soluble macrophage product was required as co-stimulator to induce sensitivity to IL4. This co-stimulator activity was unrelated to recombinant (r)IL1, rIL6 and rTNF-alpha (tumor necrosis factor alpha). In primary CD8 T cell responses rIL4-driven growth was about half of that induced by rIL2, and not inhibitable by anti-IL2 receptor antibodies. Higher concentrations of IL4 down-regulated cell proliferation. In the course of IL4-driven growth, the proliferating cells acquired sensitivity to the growth-promoting effect of IL2. Activated CD4 or CD8 T cells were found to be equally sensitive to the IL4 and IL2-driven growth pathway. Taken together, these results define a physiologic role of IL4 as growth factor during primary activation of resting CD8 T cells and thus extend the spectrum of target cells for IL4.
为了分析白细胞介素4（IL4，BSF-1）在静息（高密度）小鼠CD8 T细胞初次激活过程中的作用，使用了一种模型系统，该系统通过使用固定在琼脂糖珠上的抗T3单克隆抗体绕过抗原呈递细胞。在高细胞密度培养中，单独的IL4可诱导细胞生长，但在低细胞密度培养中则不然。在低细胞密度培养中，除了T3交联外，还需要一种可溶性巨噬细胞产物作为共刺激剂来诱导对IL4的敏感性。这种共刺激活性与重组（r）IL1、rIL6和rTNF-α（肿瘤坏死因子α）无关。在初次CD8 T细胞反应中，rIL4驱动的生长约为rIL2诱导生长的一半，且不受抗IL2受体抗体的抑制。较高浓度的IL4会下调细胞增殖。在IL4驱动的生长过程中，增殖细胞获得了对IL2促生长作用的敏感性。发现活化的CD4或CD8 T细胞对IL4和IL2驱动的生长途径同样敏感。综上所述，这些结果确定了IL4在静息CD8 T细胞初次激活过程中作为生长因子的生理作用，从而扩展了IL4的靶细胞谱。
