Colic M, Vucevic D, Vasilijic S, Popovic L, Pejanovic V, Jandric D, Medic-Mijacevic L, Rakic L
Institute of Medical Research, MMA, Belgrade, Yugoslavia.
Methods Find Exp Clin Pharmacol. 1999 Nov;21(9):583-90.
7-thia-8-oxoguanosine (immunosine) is a nucleoside analog showing efficient antiviral activity in rodent models as a consequence of enhancement of the immune response. However, little is known about the mechanisms of its action. In this work the effect of immunosine on proliferation of mouse and rat splenocytes in culture was studied. It was found that the compound stimulated proliferation of lymphocytes in a dose-dependent manner without any additional stimuli. The effect is predominantly mediated by interleukin-2 (IL-2) as judged by increased IL-2 production, upregulation of IL-2 receptor alpha (IL-2R alpha) expression and by significant inhibition (60-75%) of cell proliferation by anti-IL-2R alpha monoclonal antibodies (mAbs). Immunosine also stimulated proliferation both of T- and B-cells purified by immunomagnetic sorting. The response of B-cells was much higher than that of T-cells. The stimulatory effect of immunosine on both lymphocyte subpopulations was further increased by the addition of enriched splenic antigen-presenting cells or purified dendritic cells. Proliferation of purified T-cells to immunosine was also significantly potentiated by an anti-alpha beta T-cell receptor mAb (R 73). All these data suggest that T-, B- and accessory cells in splenic cultures are the targets of immunosine action.
7-硫代-8-氧代鸟苷（免疫肌苷）是一种核苷类似物，在啮齿动物模型中由于免疫反应增强而表现出高效的抗病毒活性。然而，其作用机制尚不清楚。在这项工作中，研究了免疫肌苷对培养的小鼠和大鼠脾细胞增殖的影响。发现该化合物在没有任何额外刺激的情况下以剂量依赖性方式刺激淋巴细胞增殖。通过增加白细胞介素-2（IL-2）的产生、上调IL-2受体α（IL-2Rα）的表达以及抗IL-2Rα单克隆抗体（mAb）对细胞增殖的显著抑制（60-75%）判断，该作用主要由IL-2介导。免疫肌苷还刺激了通过免疫磁珠分选纯化的T细胞和B细胞的增殖。B细胞的反应比T细胞高得多。通过添加富集的脾抗原呈递细胞或纯化的树突状细胞，免疫肌苷对两个淋巴细胞亚群的刺激作用进一步增强。抗αβT细胞受体mAb（R 73）也显著增强了纯化T细胞对免疫肌苷的增殖。所有这些数据表明，脾培养中的T细胞、B细胞和辅助细胞是免疫肌苷作用的靶点。
