Merino F, Alvarez-Mon M, de la Hera A, Alés J E, Bonilla F, Durantez A
Service of Internal Medicine I, Clínica Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
Cell Immunol. 1989 Feb;118(2):328-36. doi: 10.1016/0008-8749(89)90381-x.
The steroid hormone 1 alpha, 25-dihydroxyvitamin D3, calcitriol, is crucial in calcium homeostasis. Calcium plays a central role in T, B, and NK cell functions, and calcitriol is a known inhibitor of T cell proliferation and immunoglobulin production. We have analyzed here the immunoregulatory effects of calcitriol on NK cell function. We show that calcitriol specifically specifically inhibits, in a time- and dose-dependent fashion, the generation of cytotoxic activity from cultured CD16+ peripheral blood NK cells. It also suppresses, at similar molar concentrations (1-10 nM), interleukin 2 (IL-2) production by PHA-activated peripheral blood lymphocytes. Calcitriol does not interfere with the cytotoxic function of NK cells, whether fresh or generated in vitro, placing the inhibition at the level of NK cell activation. Interestingly enough, exogenous IL-2 can completely reverse the suppressive effect. These findings suggest that modulation of NK cell activation by control of the internal level of IL-2 may reflect an additional paracrine calcitriol-dependent circuit with immunoregulatory consequences.
类固醇激素1α,25 - 二羟基维生素D3（骨化三醇）在钙稳态中至关重要。钙在T细胞、B细胞和自然杀伤（NK）细胞功能中起核心作用，而骨化三醇是已知的T细胞增殖和免疫球蛋白产生的抑制剂。我们在此分析了骨化三醇对NK细胞功能的免疫调节作用。我们发现，骨化三醇以时间和剂量依赖性方式特异性抑制培养的CD16 +外周血NK细胞产生细胞毒性活性。它还在相似的摩尔浓度（1 - 10 nM）下抑制PHA激活的外周血淋巴细胞产生白细胞介素2（IL - 2）。骨化三醇不干扰NK细胞的细胞毒性功能，无论其是新鲜的还是体外产生的，表明其抑制作用发生在NK细胞激活水平。有趣的是，外源性IL - 2可以完全逆转这种抑制作用。这些发现表明，通过控制IL - 2的内源性水平来调节NK细胞激活可能反映了一种额外的、依赖骨化三醇的旁分泌回路，并具有免疫调节作用。
