低剂量白细胞介素 2 用于非人类灵长类动物体内 CD4+和 CD8+调节性 T 细胞的扩增。
Low-dose IL-2 for In vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates.
机构信息
Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
出版信息
Am J Transplant. 2012 Sep;12(9):2532-7. doi: 10.1111/j.1600-6143.2012.04133.x. Epub 2012 Jun 8.
Abstract
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 (1 million IU/m(2) 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 preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation.
摘要
白细胞介素 2（IL-2）是一种已知的强效 T 细胞生长因子，可在体内增强淋巴细胞的反应。这种能力导致高剂量白细胞介素 2 被用于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，白细胞介素 2 对于调节性 T 细胞（Tregs）的发育和外周扩展也至关重要。在本研究中，低剂量白细胞介素 2（100 万 IU/m2BSA/天）被用于在新生非人类灵长类动物体内扩增 Tregs。我们的研究表明，低剂量白细胞介素 2 治疗可显著扩增体内外周血 CD4+和 CD8+Tregs，而非 Treg 细胞的扩增有限。这些扩增的 Tregs 主要是 CD45RA（-）Foxp3（高）活化的 Tregs，并且在体外具有很强的免疫抑制功能。这项临床前研究的结果可以为 Treg 免疫疗法的发展提供基础，这种疗法在器官/细胞移植中具有重要的治疗潜力。
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