Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells.
Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells.
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1型糖尿病患者的雷帕霉素单药治疗可修饰CD4+CD25+FOXP3+调节性T细胞。
DOI：
10.2337/db08-0138
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发表时间：
2008-09
期刊：
影响因子：
7.7
通讯作者：
Battaglia, Manuela
中科院分区：
文献类型：
--
作者：
Monti, Paolo;Scirpoli, Miriam;Maffi, Paola;Piemonti, Lorenzo;Secchi, Antonio;Bonifacio, Ezio;Roncarolo, Maria-Grazia;Battaglia, Manuela
目的：雷帕霉素是一种免疫抑制药物，目前用于预防人类移植排斥反应，被认为是允许耐受诱导的。雷帕霉素允许小鼠和人类自然产生的CD4+CD25+FOXP3+ T调节细胞（nTregs）的扩增，这些细胞对于诱导和维持外周耐受性至关重要。临床前小鼠模型表明，雷帕霉素在体内也能增强nTreg的增殖和调节功能。本研究的目的是评估雷帕霉素是否对人体内的nTregs有影响。研究设计和方法：在胰岛移植前接受雷帕霉素单药治疗的一组独特的1型糖尿病患者中检测了ntreg的数量和功能。结果：我们发现雷帕霉素单药治疗并没有改变循环nTregs的频率和功能特征，即增殖和细胞因子的产生。然而，与治疗前相比，从接受雷帕霉素治疗的1型糖尿病患者中分离的nTregs抑制CD4+CD25−效应t细胞增殖的能力增强。结论-这些发现表明，雷帕霉素在体内直接影响人nTreg细胞的功能，通过改变其抑制活性，而不直接改变效应t细胞的功能。
OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4+CD25+FOXP3+ T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs. RESEARCH DESIGN AND METHODS—nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation. RESULTS—We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4+CD25− effector T-cells compared with that before treatment. CONCLUSIONS—These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function.
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CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.
影响因子：
4.4
作者：
Masteller, EL;Warner, MR;Bluestone, JA
通讯作者：
Bluestone, JA
影响因子：
7.7
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
通讯作者：
Atkinson, MA
影响因子：
12.8
作者：
Putnam, AL;Vendrame, F;Gottlieb, PA
通讯作者：
Gottlieb, PA