IMMUNOSUPPRESSIVE PROPERTIES OF 1,25-DIHYDROXYVITAMIN D3

维生素D的活性代谢物1，25-（OH）2-D3是众所周知的 钙稳态的调节剂。近年来， 发现了多种1，25-（OH）2-D3受体， 恶性和非恶性细胞的研究促使人们对 激素对这些细胞的潜在影响。 存在 这种受体在激活的人类淋巴细胞上的作用使我们发现， 以下意见。 当外周血单个核细胞 在体外用凝集素或抗原激活， 在用以下物质孵育的细胞中观察到DNA合成的抑制 1，25-（OH）2-D3，浓度范围为10-10至10-7 M。 IgG和IgM的产生，通过酶联免疫法测定 免疫吸附测定，同样受到抑制，增加 激素的浓度。 进一步研究， 淋巴细胞亚群显示T辅助细胞（TH）是 特异性细胞靶点的免疫抑制作用的1，25- （OH）2-D3。 在两种T细胞依赖性自身免疫动物模型中， 实验性变态反应性脑脊髓炎（EAE）和小鼠 间质性肾炎，辅助性T细胞克隆 表型可以被分离并显示出发挥生物活性 在体外和体内。 在人类中，T细胞克隆可以产生 来自具有HLA-DR特异性的排斥同种异体移植物的淋巴细胞。 鉴于这些发现，我们建议进一步评估 1，25-（OH）2-D3的免疫调节作用，通过评估（1）能力 1，25-（OH）2-D3干扰性能和功能 T细胞克隆的特征：增殖，淋巴因子 产生、辅助或抑制功能、疾病转移 活性和迟发型超敏反应，以及（2） 1，25-（OH）2-D3处理的小鼠受体被保护免受 主动诱导EAE和鼠间质性肾炎或从 自身免疫性疾病通过T细胞克隆的被动转移。 我们相信这项工作将促进我们对细胞和 受活性维生素D代谢物影响的体液机制， 潜在的免疫抑制剂。

The active metabolite of vitamin D, 1,25-(OH)2-D3, is a well known modulator of calcium homeostasis in man. In recent years, the discovery of specific 1,25-(OH)2-D3 receptors on a variety of malignant and non-malignant cells has prompted an investigation of the potential effect of the hormone on these cells. The presence of such receptors on activated human lymphocytes led us to the following observations. When peripheral human mononuclear cells were activated with lectins or antigen in vitro, a dose-dependent inhibition of DNA synthesis was observed in cells incubated with 1,25-(OH)2-D3 in concentrations ranging from 10-10 to 10-7 M. Production of IgG and IgM, determined by enzyme-linked immunosorbent assay, was similarly inhibited by increasing concentrations of the hormone. Further studies examining lymphocyte subsets revealed the T helper cell (TH) to be the specific cellular target for the immunoinhibitory effect of 1,25- (OH)2-D3. In two T cell dependent animal models of autoimmunity, experimental allergic encephalomyelitis (EAE) and murine interstitial nephritis, specific T cell clones of the helper phenotype can be isolated and shown to exert biological activities in vitro and in vivo. In humans, T cell clones can be generated from lymphocytes of rejected allografts with HLA-DR specificities. In light of these findings, we propose to further evaluate the immunoregulation role of 1,25-(OH)2-D3 by assessing (1) the ability of 1,25-(OH)2-D3 to interfere with the properties and functional characteristics of the T cell clones: proliferation, lymphokine production, helper or suppressor function, transfer of disease activity and delayed-type hypersensitivity and (2) the ability of 1,25-(OH)2-D3 treated murine recipients to be protected from the active induction of EAE and murine interstitial nephritis or from the passive transfer of the autoimmune diseases by T cell clones. We believe this work will advance our understanding of cellular and humoral mechanisms affected by the active vitamin D metabolite, a potential immunosuppressive agent.