van Wijk F, Wehrens E J M, Nierkens S, Boon L, Kasran A, Pieters R, Knippels L M J
Wilhelmina Children's Hospital, Department of Pediatric Immunology, and Institute for Risk Assessment Sciences, Department of Immunotoxicology, Utrecht University, Utrecht, The Netherlands.
Clin Exp Allergy. 2007 Apr;37(4):572-81. doi: 10.1111/j.1365-2222.2007.02681.x.
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a critical role in the maintenance of self-tolerance and it has been suggested that these Tregs may also be involved in preventing allergic disease.
The precise role of CD4+CD25+ T cells in the regulation of allergic responses to mucosal antigens remains to be elucidated. In the present study, it was investigated whether CD4+CD25+ T cells are involved in the induction of oral tolerance and whether they play a role in controlling hypersensitivity responses to food proteins.
CD4+CD25+ T cells were depleted with PC61 mAb before the induction of low dose oral tolerance to peanut extract (PE). In addition, CD4+CD25+ T cell depletion was performed during sensitization or before oral challenge, using a C3H/HeOuJ mouse model of allergic sensitization to peanut.
Oral tolerance to PE could not be induced in CD4+CD25+ T cell-depleted mice. However, CD4+CD25+ T cell depletion during long-term exposure to PE alone did not result in allergic sensitization. In sensitized mice, anti-CD25 treatment during oral exposure resulted in higher levels of PE-specific IgE and increased mast cell degranulation upon an oral challenge. In contrast, anti-CD25 treatment of PE-sensitized mice before oral challenges did not affect the level of mast cell degranulation.
These results indicate that CD4+CD25+ Tregs are involved in maintaining tolerance to oral antigens and regulate the intensity of an IgE-mediated food hypersensitivity response, but are not crucial in preventing sensitization. Accordingly, CD4+CD25+ Tregs may represent a potential tool for the treatment of food allergic disorders.
天然存在的CD4+CD25+调节性T细胞（Tregs）在维持自身耐受性方面发挥着关键作用，并且有人提出这些Tregs也可能参与预防过敏性疾病。
CD4+CD25+ T细胞在调节对黏膜抗原的过敏反应中的精确作用仍有待阐明。在本研究中，研究了CD4+CD25+ T细胞是否参与口服耐受性的诱导以及它们在控制对食物蛋白的超敏反应中是否发挥作用。
在用花生提取物（PE）诱导低剂量口服耐受性之前，用PC61单克隆抗体清除CD4+CD25+ T细胞。此外，使用对花生过敏致敏的C3H/HeOuJ小鼠模型，在致敏期间或口服激发前进行CD4+CD25+ T细胞清除。
在清除CD4+CD25+ T细胞的小鼠中无法诱导对PE的口服耐受性。然而，仅在长期暴露于PE期间清除CD4+CD25+ T细胞并不会导致过敏致敏。在致敏小鼠中，口服暴露期间的抗CD25治疗导致更高水平的PE特异性IgE，并在口服激发时增加肥大细胞脱颗粒。相比之下，在口服激发前对PE致敏小鼠进行抗CD25治疗并不影响肥大细胞脱颗粒水平。
这些结果表明，CD4+CD25+ Tregs参与维持对口服抗原的耐受性并调节IgE介导的食物超敏反应的强度，但在预防致敏方面并非至关重要。因此，CD4+CD25+ Tregs可能代表一种治疗食物过敏疾病的潜在工具。
