Low-dose IL-2 for In vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates.

Low-dose IL-2 for In vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates.
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DOI:
10.1111/j.1600-6143.2012.04133.x
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发表时间:
2012-09
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Kawai T
Kawai T
中科院分区:
其他
文献类型:
--
作者:
Aoyama A;Klarin D;Yamada Y;Boskovic S;Nadazdin O;Kawai K;Schoenfeld D;Madsen JC;Cosimi AB;Benichou G;Kawai T

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IL-2是一种已知的强效T细胞生长因子,可在体内放大淋巴细胞反应。这种能力导致使用高剂量IL-2来增强艾滋病或癌症患者的T细胞免疫。然而,最近的研究表明,IL-2对于调节性T细胞(Tregs)的发育和外周扩增也至关重要。在目前的研究中,给药低剂量IL-2(100万单位/m2 BSA/天)在naïve非人灵长类动物体内扩增Tregs。我们的研究表明,低剂量IL-2治疗显著增加了体内外周血CD4+和CD8+ treg细胞,而非treg细胞的扩增有限。这些扩增的treg主要是CD45RA- Foxp3高激活treg,在体外显示出强大的免疫抑制功能。本临床前研究结果可作为开发Treg免疫疗法的基础,Treg免疫疗法在器官/细胞移植中具有重要的治疗潜力。
IL-2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high dose IL-2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL-2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low dose IL-2 (1million unit/m2 BSA/day) was administered to expand Tregs in vivo in naïve nonhuman primates. Our study demonstrated that low dose IL-2 therapy significantly expanded peripheral blood CD4+ and CD8+ Tregs in vivo with limited expansion of non-Treg cells. These expanded Tregs are mainly CD45RA- Foxp3 high activated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this pre-clinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation.
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