Bulgarini D, Scalzo S, Boccoli G, Petrini M, Quaranta M T, Camagna A, Isacchi G, Testa U, Peschle C
Department of Hematology and Oncology, Istituto Superiore di Sanità, Roma, Italy.
J Biol Regul Homeost Agents. 1991 Jan-Mar;5(1):23-33.
IL-6 preferentially promotes the DNA synthesis of human peripheral blood CD8+, rather than CD4+, lymphocytes in presence of PHA: this effect is observed in serum-free cultures of greater than 99% purified CD8+ lymphocytes. However, IL-6 is able to stimulate DNA synthesis of CD8+ lymphocytes triggered by a mitogenic anti-CD2 mAb, but not by anti-CD3 mAb: these results suggest that IL-6 selectively induces activation of CD8+ lymphocytes through the CD2 rather than the CD3 pathway. Limiting dilution analysis indicates that accessory cells are not required to mediate the action of IL-6 on CD8+ cells. Furthermore, this action is not blocked by addition of mAb neutralizing either IL-2 or IL2R, thus suggesting that IL-6 does not act via IL-2. CD8+ lymphocytes grown in the presence of PHA + IL-6 incorporate (3H)-thymidine to the same extent as those stimulated with PHA + IL-2, but do not increase in number until day 6 of culture. It is hence apparent that the stimulating activity of IL-6 on CD8+ lymphocytes is restricted to the GO----S phase progression, but does not lead to mitosis. IL-6 receptors are expressed on resting CD4+ and CD8+ lymphocytes: their expression is significantly enhanced on both activated CD4+ and CD8+ cells. Scatchard analysis of (125I)-IL-6 binding data showed the presence of high (Kd, 3 x 10(-10) M) and low (Kd, 6 x 10(-8) M) affinity IL6R on both lymphocyte populations. Similarly, mRNA encoding IL6R was detected in both CD4+ and CD8+ lymphocytes. Thus, our studies indicate that IL-6 directly and selectively stimulates the GO----S progression of CD8+ lymphocytes in the presence of mitogen and absence of IL-2: this phenomenon may be of interest for the elucidation of mechanisms activating cytotoxic T lymphocytes.
在存在PHA的情况下，IL-6优先促进人外周血CD8⁺而非CD4⁺淋巴细胞的DNA合成：在纯度大于99%的CD8⁺淋巴细胞的无血清培养物中可观察到这种效应。然而，IL-6能够刺激由促有丝分裂抗CD2单克隆抗体触发的CD8⁺淋巴细胞的DNA合成，但不能刺激由抗CD3单克隆抗体触发的DNA合成：这些结果表明IL-6通过CD2而非CD3途径选择性地诱导CD8⁺淋巴细胞的活化。有限稀释分析表明，辅助细胞并非介导IL-6对CD8⁺细胞作用所必需。此外，添加中和IL-2或IL-2R的单克隆抗体并不能阻断这种作用，因此表明IL-6并非通过IL-2发挥作用。在PHA + IL-6存在下生长的CD8⁺淋巴细胞掺入（³H）-胸苷的程度与用PHA + IL-2刺激的细胞相同，但直到培养第6天数量才增加。因此很明显，IL-6对CD8⁺淋巴细胞的刺激活性仅限于G₀期向S期的进展，但不会导致有丝分裂。IL-6受体在静止的CD4⁺和CD8⁺淋巴细胞上表达：在活化的CD4⁺和CD8⁺细胞上其表达均显著增强。对（¹²⁵I）-IL-6结合数据的Scatchard分析表明，在这两种淋巴细胞群体上均存在高亲和力（Kd，3×10⁻¹⁰ M）和低亲和力（Kd，6×10⁻⁸ M）的IL-6R。同样，在CD4⁺和CD8⁺淋巴细胞中均检测到编码IL-6R的mRNA。因此，我们的研究表明，在有丝分裂原存在且无IL-2的情况下，IL-6直接且选择性地刺激CD8⁺淋巴细胞从G₀期向S期进展：这一现象对于阐明激活细胞毒性T淋巴细胞的机制可能具有重要意义。
