Warner G L, Lawrence D A
Department of Microbiology and Immunology, Albany Medical College of Union University, New York 12208.
Int J Immunopharmacol. 1988;10(5):629-37. doi: 10.1016/0192-0561(88)90082-3.
The heavy metals Pb, Ni and Zn have previously been demonstrated to stimulate the proliferation of an Lyt1+2-, L3T4+T-cell. This proliferation required the presence of Ia+ cells and was blocked by monoclonal antibodies directed against self I-A, self I-E and L3T4a. The work reported here examined the role of T-cell factors (IL-2 and gamma-IFN) and their receptors in the metal-induced lymphoproliferation. The metals Pb, Ni and Zn, at concentrations (100 microM) which stimulate T-cell proliferation, had little effect on the ability of the IL-2-dependent cell line HT-2 to respond to exogenous IL-2. This suggests that Pb, Ni and Zn do not modulate the ability of IL-2 to interact with the IL-2 receptor. Ni and Zn significantly enhanced the synthesis/secretion of IL-2 by cultured splenocytes and the expression of the receptor for IL-2; however, Pb produced only slight enhancement. Likewise, anti-IL-2 receptor (7D4) antibodies were able to inhibit a significant portion of the Ni- and Zn-, but not Pb-, induced lymphoproliferation. The residual 3H-thymidine incorporation observed in the presence of anti-IL-2 and anti-IL-2R may represent cycling B-cells induced to proliferate by activated, but non-cyclin, T-cells. Monoclonal anti-gamma-IFN (R4/6A2) equally inhibited all metal-induced lymphoproliferation, suggesting that metal-induced lymphoproliferation is dependent on the induction of gamma-IFN as well as IL-2 synthesis. The Pb-induced response being the least dependent on IL-2 lends support to the hypothesis that Pb, Ni and Zn may activate T-cells and/or B-cells by different mechanisms.
重金属铅、镍和锌先前已被证明能刺激Lyt1 + 2 -、L3T4 + T细胞的增殖。这种增殖需要Ia + 细胞的存在，并被针对自身I - A、自身I - E和L3T4a的单克隆抗体所阻断。本文报道的工作研究了T细胞因子（IL - 2和γ - 干扰素）及其受体在金属诱导的淋巴细胞增殖中的作用。铅、镍和锌在刺激T细胞增殖的浓度（100微摩尔）下，对IL - 2依赖细胞系HT - 2对外源IL - 2的反应能力影响很小。这表明铅、镍和锌不会调节IL - 2与IL - 2受体相互作用的能力。镍和锌显著增强了培养的脾细胞中IL - 2的合成/分泌以及IL - 2受体的表达；然而，铅仅产生轻微增强。同样，抗IL - 2受体（7D4）抗体能够抑制镍和锌诱导的淋巴细胞增殖的很大一部分，但不能抑制铅诱导的增殖。在存在抗IL - 2和抗IL - 2R的情况下观察到的残余3H - 胸腺嘧啶核苷掺入可能代表由活化但非细胞周期蛋白的T细胞诱导增殖的循环B细胞。单克隆抗γ - 干扰素（R4 / 6A2）同样抑制所有金属诱导的淋巴细胞增殖，表明金属诱导的淋巴细胞增殖依赖于γ - 干扰素的诱导以及IL - 2的合成。铅诱导的反应对IL - 2的依赖性最小，这支持了铅、镍和锌可能通过不同机制激活T细胞和/或B细胞的假设。
