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抗炎类固醇对T细胞介导的细胞毒性的抑制作用。

Inhibition of T cell-mediated cytotoxicity by anti-inflammatory steroids.

作者信息

Schleimer R P, Jacques A, Shin H S, Lichtenstein L M, Plaut M

出版信息

J Immunol. 1984 Jan;132(1):266-71.

PMID:6606668
Abstract

We have tested the capacity of glucocorticoids to modulate the effector function of splenic cytotoxic T lymphocytes (CTL) obtained after i.p. immunization with allogeneic cells. Although acute exposure to glucocorticoids did not inhibit the activity of freshly obtained splenic CTL, preincubation of these CTL for several hours with subnanomolar concentrations of several different glucocorticoids caused marked inhibition. The relative inhibitory potency of the steroids tested correlated with their reported activity both in glucocorticoid receptor binding assays and in assays of anti-inflammatory potency in man. The inhibitory effects of low concentrations (10(-10) M to 10(-9) M) of dexamethasone were reversed by human or mouse interleukin 2 (IL 2)-containing supernatants, but were not reversed by IL 1-containing supernatants. The inhibitory effects of higher concentrations (10(-8) M to 10(-7) M) of dexamethasone could not be reversed even by very high doses of mouse IL 2. In contrast to previous reports of minimal direct glucocorticoid effects on CTL activity, the present results suggest that after preincubation, splenic CTL from in vivo-immune mice are sensitive to inhibition by glucocorticoids, and that the glucocorticoids may act both indirectly (on IL 2 production) and directly on the CTL.

摘要

我们检测了糖皮质激素调节经腹腔注射同种异体细胞免疫后获得的脾细胞毒性T淋巴细胞(CTL)效应功能的能力。虽然急性暴露于糖皮质激素并未抑制新鲜获得的脾细胞CTL的活性,但用几种不同糖皮质激素的亚纳摩尔浓度对这些CTL进行数小时的预孵育会导致明显抑制。所测试类固醇的相对抑制效力与其在糖皮质激素受体结合试验以及人体抗炎效力试验中报道的活性相关。低浓度(10⁻¹⁰M至10⁻⁹M)地塞米松的抑制作用可被含人或小鼠白细胞介素2(IL-2)的上清液逆转,但不能被含IL-1的上清液逆转。即使是非常高剂量的小鼠IL-2也无法逆转高浓度(10⁻⁸M至10⁻⁷M)地塞米松的抑制作用。与之前关于糖皮质激素对CTL活性的直接影响极小的报道相反,目前的结果表明,在预孵育后,来自体内免疫小鼠的脾细胞CTL对糖皮质激素的抑制敏感,并且糖皮质激素可能既间接作用(对IL-2产生)又直接作用于CTL。

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Inhibition of T cell-mediated cytotoxicity by anti-inflammatory steroids.抗炎类固醇对T细胞介导的细胞毒性的抑制作用。
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