Eusebio M, Kuna P, Kraszula L, Kupczyk M, Pietruczuk M
Department of Laboratory Diagnostics, Medical University of Lodz, Poland.
Department of Internal Medicine, Medical University of Lodz, Poland.
J Biol Regul Homeost Agents. 2014 Jul-Sep;28(3):461-70.
There is an increasing body of evidence that alterations of regulatory T (Treg) cell numbers and functions lead to immune disorders. Accordingly, understanding the regulatory mechanisms that maintain peripheral regulatory T (Treg) cell homeostasis is key to the development of effective targeted biologic therapies. We previously demonstrated the effects of IL-10 or TGF-beta on distinct CD8+CD28- T cell subsets in vitro. Allergy-related changes of CD8+CD25+FoxP3(bright)Treg cells and FoxP3 mRNA expression in peripheral blood were assessed by means of multicolor flow cytometry and real-time polymerase chain reaction (RT-PCR). Co-stimulation of CD8+CD25+ T cells with anti-CD3/CD28 in the presence of either IL-10 or TGF-beta increased the frequency of CD8+CD25+FoxP3(bright)Treg cells in patients with asthma and controls. Likewise, CD8+CD25+ T cell activation with anti-CD3/CD28 and TGF-beta increased FoxP3mRNA expression in all groups. Anti-CD3/CD28 and IL-10 appeared to regulate FoxP3 mRNA expression in a phenotype-dependent manner. Specifically, co-stimulation by anti-CD3/CD28 and IL-10 markedly increased FoxP3 mRNA expression in the severe asthma group whereas it had opposite effects on this value in other groups. Taken altogether, these data suggest that IL-10 and TGF-beta may modulate FoxP3 expressions at the protein and mRNA levels in respect to their need for peripheral tolerance.
越来越多的证据表明，调节性T（Treg）细胞数量和功能的改变会导致免疫紊乱。因此，了解维持外周调节性T（Treg）细胞稳态的调节机制是开发有效的靶向生物疗法的关键。我们之前在体外证明了白细胞介素-10（IL-10）或转化生长因子-β（TGF-β）对不同的CD8 + CD28 - T细胞亚群的影响。通过多色流式细胞术和实时聚合酶链反应（RT-PCR）评估外周血中CD8 + CD25 + FoxP3（明亮）Treg细胞的过敏相关变化和FoxP3 mRNA表达。在存在IL-10或TGF-β的情况下，用抗CD3/CD28共刺激CD8 + CD25 + T细胞可增加哮喘患者和对照组中CD8 + CD25 + FoxP3（明亮）Treg细胞的频率。同样，用抗CD3/CD28和TGF-β激活CD8 + CD25 + T细胞可增加所有组中的FoxP3mRNA表达。抗CD3/CD28和IL-10似乎以表型依赖的方式调节FoxP3 mRNA表达。具体而言，抗CD3/CD28和IL-10的共刺激在重度哮喘组中显著增加了FoxP3 mRNA表达，而在其他组中对该值有相反的影响。综上所述，这些数据表明，IL-10和TGF-β可能根据外周耐受的需要在蛋白质和mRNA水平上调节FoxP3表达。
