Jung S, Toyka K V, Hartung H P
Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
Clin Exp Immunol. 1994 Dec;98(3):494-502. doi: 10.1111/j.1365-2249.1994.tb05518.x.
The influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen- or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG. Like activation-induced T cell proliferation, IL-2-dependent growth of CD4+ T line cells was not affected by DSG. Preincubation of CD4+ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T cell receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.
在体外和体内分析了免疫抑制抗生素15 - 脱氧精胍菌素（DSG）对Lewis大鼠巨噬细胞和自身反应性辅助性T淋巴细胞的影响。DSG在体外不抑制致脑炎或致神经炎辅助性T细胞系的抗原或丝裂原诱导的增殖。然而，在T细胞体外激活过程中存在DSG时，尽管T系母细胞上的激活标志物或黏附分子的表达未被DSG下调，但在将其过继转移至未致敏大鼠后，其诱导脑炎（EAE）或神经炎（EAN）的能力被强烈抑制或完全消除。与激活诱导的T细胞增殖一样，CD4 + T系细胞的IL - 2依赖性生长不受DSG影响。然而，在IL - 2驱动的增殖过程中，将CD4 + T系细胞在DSG中预孵育48小时，可抑制这些T细胞随后的抗原诱导激活，但不抑制丝裂原诱导的激活，尽管暴露于DSG的细胞上T细胞受体的密度以及参与抗原识别的其他表面分子均未降低。与其在体外的作用相似，即使以具有累积毒性的浓度在体内给予DSG 10天，也不会抑制丝裂原或抗CD2抗体的丝裂原组合诱导的脾细胞体外增殖。此外，长期用DSG处理30天不会改变脾细胞和外周血淋巴细胞（PBL）的表面抗原，特别是MHC分子。虽然这两个群体中的多形核细胞数量略有减少，但不同白细胞亚群的比例保持不变。与DSG对自身反应性辅助性T细胞的强大功能影响相反，该药物不抑制巨噬细胞的氧化爆发或其MHC抗原表达。这项研究证明了DSG对CD4 + T淋巴细胞有明显的抑制作用，但对巨噬细胞没有抑制作用。这为最近观察到的DSG在体内对移植排斥和实验性自身免疫性疾病有强大的免疫抑制作用提供了解释，尽管体内和体外暴露于DSG的T细胞的丝裂原反应正常。
