Glucocorticoid-Induced Inhibition of T Cell Growth Factor Production
Glucocorticoid-Induced Inhibition of T Cell Growth Factor Production
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糖皮质激素诱导的 T 细胞生长因子产生抑制
DOI：
10.4049/jimmunol.123.4.1632
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
Kendall A. Smith
中科院分区：
文献类型：
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作者：
S. Gillis;G. Crabtree;Kendall A. Smith
先前的通信提供的数据详细说明了糖皮质激素对长期T细胞生长因子（TCGF）依赖性培养物中维持的溶细胞性T细胞的增殖表现出轻微但显著的抑制作用。然而，最重要的是，糖皮质激素显示通过对TCGF产生的深刻影响来抑制T淋巴细胞增殖。糖皮质激素处理的人，小鼠或大鼠的T细胞有丝分裂原刺激的淋巴细胞添加外源性TCGF恢复正常的增殖水平。这些观察使我们提出糖皮质激素的免疫抑制作用是通过控制T细胞增殖诱导剂TCGF的产生来介导的。
本文中详细介绍的实验结果为支持这一假设提供了进一步的证据。我们发现，虽然糖皮质激素对从TCGF依赖性培养物中收获的T细胞的细胞溶解反应性几乎没有影响，但用相同糖皮质激素浓度处理混合淋巴细胞培养物（MLC）完全废除了原位TCGF产生和同种抗原定向细胞溶解。延迟加入外源性TCGF可再次消除糖皮质激素对MLC的抑制作用。这些观察结果与先前报告中详细描述的结果相结合，提供了证据表明，糖皮质激素不是影响潜在反应性成熟淋巴细胞的裂解，而是通过抑制TCGF产生来影响T细胞介导的免疫反应性的发展，这反过来又抑制了活化T细胞的克隆扩增。
The previous communication presented data detailing that glucocorticoid hormones exhibited slight but significant inhibitory effects on the proliferation of cytolytic T cells maintained in long-term T cell growth factor (TCGF)-dependent cultures. However, most importantly, glucocorticoids were shown to inhibit T-lymphocyte proliferation via a profound effect on TCGF production. Addition of exogenous TCGF to glucocorticoid-treated human, mouse, or rat T cell mitogen-stimulated lymphocytes restored normal levels of proliferation. These observations led us to propose that the immunosuppressive effects of glucocorticoid hormones were mediated by controlling the production of the T cell proliferation-inducing agent, TCGF.
Results of experimentation detailed in this communication provide further evidence in support of this hypothesis. We found that although glucocorticoid hormones had little effect on the cytolytic reactivity of T cells harvested from TCGF-dependent culture, treatment of mixed lymphocyte cultures (MLC) with identical glucocorticoid hormone concentrations completely abrogated in situ TCGF production and alloantigen-directed cytolysis. The inhibitory effects of glucocorticoids in MLC could be eliminated once again simply by the delayed addition of exogenous TCGF. These observations coupled with those detailed in the previous report provide evidence that, rather than effecting lysis of potentially reactive mature lymphocytes, glucocorticoids influence the development of T cell-mediated immune reactivity by inhibiting TCGF production, which in turn serves to inhibit the clonal expansion of activated T cells.