Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice
Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice
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DOI：
10.4049/jimmunol.175.5.3053
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Bluestone, JA
中科院分区：
文献类型：
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作者：
Masteller, EL;Warner, MR;Bluestone, JA
CD（4+）CD 25（+）Foxp（3+）调节性T细胞（T-reg）对于控制自身免疫至关重要。有证据表明，T-reg的发育、外周维持和抑制功能取决于抗原特异性。然而，几乎没有直接证据表明负责控制NOD小鼠或其他自然环境中自身免疫的T-reg是Ag特异性的。事实上，一些研究者认为多克隆Ag-非特异性T-reg是免疫的有效调节剂。因此，本研究的目的是确定，扩大和表征胰岛Ag特异性T-reg在NOD小鼠。使用IL-2和用重组胰岛肽模拟物-MHC II类和抗CD 28 mAb包被的珠粒在体外有效地扩增来自NOD小鼠的Ag特异性Treg。扩增的Ag特异性T-reg表达原型表面标志物和细胞因子。尽管以Ag特异性方式激活，但扩增的T-reg能够在体外和体内进行旁观者抑制。重要的是，胰岛肽模拟物特异性T-reg在抑制自身免疫性糖尿病方面比多克隆Treg更有效。这些结果提供了在自然环境中存在自身抗原特异性T-reg的直接证明，其可用作器官特异性自身免疫的治疗剂。
CD(4+)CD25(+)Foxp(3+) regulatory T cells (T-reg) are critical for controlling autoinummity. Evidence suggests that T-reg development, peripheral maintenance, and suppressive function are dependent on Ag specificity. However, there is little direct evidence that the T-reg responsible for controlling autoimmunity in NOD mice or other natural settings are Ag specific. In fact, some investigators have argued that polyclonal Ag-nonspecific T-reg are efficient regulators of immunity. Thus, the goal of this study was to identify, expand, and characterize islet Ag-specific T-reg in NOD mice. Ag-specific Treg from NOD mice were efficiently expanded in vitro using IL-2 and beads coated with recombinant islet peptide mimic-MHC class II and anti-CD28 mAb. The expanded Ag-specific T-reg expressed prototypic surface markers and cytokines. Although activated in an Ag-specific fashion, the expanded T-reg were capable of bystander suppression both in vitro and in vivo. Importantly, the islet peptide mimic-specific T-reg were more efficient than polyclonal Treg in suppressing autoimmune diabetes. These results provide a direct demonstration of the presence of autoantigen-specific T-reg in the natural setting that can be applied as therapeutics for organ-specific autoimmunity.