Institute for Risk Assessment Sciences, Utrecht University, Utrecht.
Allergy. 2011 Mar;66(3):331-40. doi: 10.1111/j.1398-9995.2010.02479.x. Epub 2010 Sep 29.
Food allergy affects approximately 5% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. The mucosal adjuvant cholera toxin induces allergic sensitization to co-administered proteins in mice, while feeding the protein alone induces oral tolerance. Intestinal γδ T cells could be of importance in the induction of oral tolerance. This study aims to investigate whether γδ T cells have functional relevance in food allergic sensitization.
Changes in γδ T cells on days 1, 2, 3, and 7 after initiation of food allergy were evaluated using flowcytometry. Furthermore, the anti-γδ T-cell receptor (TCR) antibody UC7 was used to block the γδ TCR in mice in vivo, followed by sensitization to peanut. After 4 weeks, peanut-specific antibodies in serum and cytokine production in spleen were measured.
Induction of food allergy resulted in a profound decrease in the percentage of γδ T cells in intestinal tissues and Peyer's Patches, but not in mesenteric lymph nodes or spleen. This decrease could be detected from days 1 to 2 after the initiation of food allergy and the number of γδ T cells returned to normal on day 7. Blockade of the γδ TCR resulted in elevated food allergic responses upon sensitization with peanut characterized by increased IgE and Th2 cytokine production in splenocytes.
These results demonstrate a unique regulatory role of γδ T cells, suggesting that targeting γδ T cells in the intestine may contribute to strategies to prevent and possibly treat food allergy.
食物过敏影响约 5%的儿童,是西方国家因过敏性反应住院的主要原因。黏膜佐剂霍乱毒素可诱导小鼠对同时给予的蛋白质产生过敏敏化,而单独给予蛋白质则可诱导口服耐受。肠道 γδ T 细胞在诱导口服耐受中可能具有重要作用。本研究旨在探讨 γδ T 细胞在食物过敏敏化中是否具有功能相关性。
通过流式细胞术评估食物过敏开始后第 1、2、3 和 7 天 γδ T 细胞的变化。此外,在体内使用抗 γδ T 细胞受体(TCR)抗体 UC7 阻断 γδ TCR,然后致敏花生。4 周后,测量血清中的花生特异性抗体和脾细胞中的细胞因子产生。
食物过敏的诱导导致肠道组织和派尔氏斑中 γδ T 细胞的百分比明显下降,但肠系膜淋巴结和脾脏中没有下降。这种下降可在食物过敏开始后第 1 天至第 2 天检测到,第 7 天 γδ T 细胞数量恢复正常。阻断 γδ TCR 导致致敏花生时食物过敏反应升高,特征为脾细胞中 IgE 和 Th2 细胞因子产生增加。
这些结果表明 γδ T 细胞具有独特的调节作用,提示靶向肠道中的 γδ T 细胞可能有助于预防和治疗食物过敏的策略。