Influence of short-term glucocorticoid therapy on regulatory T cells in vivo.
Influence of short-term glucocorticoid therapy on regulatory T cells in vivo.
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DOI：
10.1371/journal.pone.0024345
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fassnacht M
中科院分区：
文献类型：
--
作者：
Sbiera S;Dexneit T;Reichardt SD;Michel KD;van den Brandt J;Schmull S;Kraus L;Beyer M;Mlynski R;Wortmann S;Allolio B;Reichardt HM;Fassnacht M
对自身免疫性疾病患者的前期和早期临床研究表明，调节性T(Treg)细胞的诱导可能有助于糖皮质激素(GCs)的免疫抑制作用。我们重新阐述了GC治疗对具有免疫能力的人类受试者和幼稚小鼠Treg细胞的影响。小鼠静脉注射剂量递增的地塞米松，然后口服锥体，用流式细胞仪分析脾和血中的Treg细胞。16例突发性听力损失但无炎症性疾病的患者接受大剂量强的松龙静脉注射，然后逐步减量至低剂量口服强的松龙。根据不同的标记物对14天GC治疗前后的外周血Treg细胞进行分析。连续给药3d，小鼠血(100 mg地塞米松/kg体重：2.8±1.8×104个/ml，对照组33±11×104个/只)和脾(地塞米松：2.8±1.9×105个/脾，对照组95±22×105个/脾)中Treg细胞的绝对数呈剂量依赖性减少，14d后恢复缓慢，但血液中无明显变化。在CD4+T细胞中，FOXP3+Treg细胞的相对频率也以剂量依赖的方式下降，这种影响在血液中比在脾中更明显。GC体外处理不改变Treg细胞的抑制能力。在免疫功能正常的人中，GCs诱导轻度T细胞淋巴细胞增多症。然而，尽管根据Treg细胞的定义有一些变化(FOXP3+：4.0±1.5%比3.4±1.5%*；AITR+：0.6±0.4比0.5±0.3%；CD127 low：4.0±1.3比5.0±3.0%*和CTLA4+：13.8±11.5比15.6±12.5%；*p<；0.05)，但它并没有以相关的方式改变循环中Treg细胞的相对频率。短期的GC治疗不会引起迄今所认为的循环Treg细胞频率的增加，无论是在具有免疫能力的人还是在小鼠身上。因此，GCs的临床疗效是通过调节Treg细胞数量来实现的，这是值得怀疑的。
Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naïve mice. Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.8±1.8×104 cells/ml vs. 33±11×104 in control mice) and spleen (dexamethasone: 2.8±1.9×105/spleen vs. 95±22×105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.0±1.5% vs 3.4±1.5%*; AITR+: 0.6±0.4 vs 0.5±0.3%, CD127low: 4.0±1.3 vs 5.0±3.0%* and CTLA4+: 13.8±11.5 vs 15.6±12.5%; * p<0.05). Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers.
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DOI：
10.1196/annals.1321.009
发表时间：
2004-01-01
期刊：
GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS
影响因子：
--
作者：
Franchimont, D
通讯作者：
Franchimont, D
影响因子：
8.6
作者：
Azab, N. A.;Bassyouni, I. H.;Mashahit, M. A.
通讯作者：
Mashahit, M. A.
影响因子：
3.5
作者：
Banica, Leontina;Besliu, Alina;Matache, Cristiana
通讯作者：
Matache, Cristiana
影响因子：
5.4
作者：
Chen, X;Murakami, T;Howard, DMZ
通讯作者：
Howard, DMZ
影响因子：
14.2
作者：
Karagiannidis, C;Akdis, M;Schmidt-Weber, CB
通讯作者：
Schmidt-Weber, CB