Developmental Biology and Regenerative Medicine Program, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2012;7(7):e40314. doi: 10.1371/journal.pone.0040314. Epub 2012 Jul 9.
Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.
无论是天然的还是诱导产生的调节性 T（Treg）细胞，都是自身免疫和过敏疾病的有效调节剂。过敏性哮喘患者存在内源性 Treg 细胞缺陷，提示 Treg 细胞介导的免疫调节紊乱可能在气道过敏性炎症中发挥重要作用。为了确定体外诱导产生的 Treg 细胞过继转移是否可作为抑制气道过敏性炎症的有效治疗方法，在卵清蛋白致敏的小鼠接受鼻内卵清蛋白激发之前或期间输注外源性诱导的 Treg 细胞。结果表明，在过敏原攻击之前输注诱导的 Treg 细胞可显著降低气道高反应性、嗜酸性粒细胞募集、黏液高分泌、气道重塑和 IgE 水平。这种效应与引流淋巴结中 Treg 细胞（CD4(+)FoxP3(+))增加和树突状细胞减少有关，与对照相比，Th1、Th2 和 Th17 细胞反应减少。此外，在过敏原攻击期间输注诱导的 Treg 细胞也可有效减轻气道炎症并改善气道功能，与天然 Treg 细胞输注的效果相当。因此，体外诱导的 Treg 细胞过继转移可能是预防和治疗严重哮喘的一种有前途的治疗方法。
