Foxp3+ Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self. Therefore, it is expected that lower numbers and/or less than optimal function could impact on the functioning of the immune system, and thereby contributing to the development of autoimmune diseases. In the present report, by comparing Tregs from most frequently used mouse strains in immunological research (C57BL/6 (B6), BALB/c and NOD), we provide evidence showing that the NOD mouse strain, highly predisposed to develop autoimmune responses, exhibit a generalized decreased in Tregs counts with enhanced proportions of CD44hiCD62Llow Tregs when compared with BALB/c mice. No major differences were observed in Helios+ or Helios- Tregs between strains. The expression of CXCR3, CCR5 and CCR6 on Tregs from all strains showed minor proportions of CXCR3+ and CCR5+ cells in NOD Tregs. Naïve CD4+CD25- T cells from NOD mice also showed decreased capacity to induce in vitro iTregs when compared with B6 and BALB/c mice. Lower expression of molecules involved in Treg suppressor mechanisms such as CD25, LAP-1, CD39 and PD-1 was observed both in NOD iTregs and Tregs from lymph nodes of NOD mice. Moreover, in vitro assays showed that Tregs from NOD mice exhibited reduced ability to suppress proliferation of CD4+CD25- responder T cells when compared with B6 and BALB/c mice. Major differences were consistently observed between NOD and BALB/c mice, whereas no major differences were found for many of the analyzed parameters between the NOD and B6 mice, suggesting that highly and mildly autoimmune prone mouse strains may share some Tregs features. On the contrary, BALB/c Tregs were in major quantities, expressed higher levels of Foxp3 and exhibited more potent ability to inhibit effector T cell proliferation, data that could be related to its natural resistance to the induction of different experimental autoimmune conditions. Altogether our results demonstrate a generalized Treg cell dysfunction in NOD mice, a strain characterized by its high predisposition to develop spontaneous and induced autoimmune diseases.

中文翻译：

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免疫学研究中常用的小鼠品系之间的T调节细胞差异：NOD，B6和BALB / c小鼠中的Treg细胞数量和亚群。

Foxp3 +调节性T细胞（Tregs）对于维持自我耐受性至关重要。因此，期望较少的数量和/或少于最佳的功能可能影响免疫系统的功能，从而有助于自身免疫疾病的发展。在本报告中，通过比较免疫学研究中最常用的小鼠品系（C57BL / 6（B6），BALB / c和NOD）的Treg，我们提供的证据表明，高度倾向于发展自身免疫反应的NOD小鼠品系表现出与BALB / c小鼠相比，随着CD44hiCD62Llow Tregs比例的增加，Tregs计数普遍下降。在菌株之间的Helios +或Helios-Treg中未观察到主要差异。CXCR3的表达，所有菌株的Tregs上的CCR5和CCR6在NOD Tregs中显示少量的CXCR3 +和CCR5 +细胞。与B6和BALB / c小鼠相比，来自NOD小鼠的幼稚CD4 + CD25-T细胞还显示出诱导体外iTreg的能力降低。在NOD iTregs和来自NOD小鼠淋巴结的Tregs中均观察到与Treg抑制机制有关的分子（如CD25，LAP-1，CD39和PD-1）的较低表达。此外，体外试验显示，与B6和BALB / c小鼠相比，来自NOD小鼠的Tregs抑制CD4 + CD25-应答性T细胞增殖的能力降低。在NOD和BALB / c小鼠之间始终观察到主要差异，而在NOD和B6小鼠之间的许多分析参数中未发现主要差异，提示高度和轻度易自身免疫的小鼠品系可能具有某些Tregs功能。相反，BALB / c Treg大量存在，表达更高水平的Foxp3，并且表现出更强的抑制效应T细胞增殖的能力，这些数据可能与其天然诱导不同实验自身免疫条件有关。总的来说，我们的结果证明了NOD小鼠中普遍存在的Treg细胞功能异常，该菌株的特征是其易患自发性和诱发性自身免疫性疾病的易感性。可能与其天然诱导不同实验自身免疫条件有关的数据。总的来说，我们的结果证明了NOD小鼠中普遍存在的Treg细胞功能异常，该菌株的特征是其易患自发性和诱发性自身免疫性疾病的易感性。可能与其天然诱导不同实验自身免疫条件有关的数据。总的来说，我们的结果证明了NOD小鼠中普遍存在的Treg细胞功能异常，该菌株的特征是其易患自发性和诱发性自身免疫性疾病的易感性。