Knight Adina Kay, Blázquez Ana Belén, Zhang Shu, Mayer Lloyd, Sampson Hugh A, Berin M Cecilia
The Division of Allergy and Immunology/Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1234-43. doi: 10.1152/ajpgi.00323.2007. Epub 2007 Oct 4.
A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.
在患有食物过敏症的受试者的肠道中观察到了局部的Th2微环境；然而，T细胞在这些疾病病理生理学中的作用仍知之甚少。我们的目的是检查食物激发后T细胞活化的部位，确定负责T细胞募集到肠道的潜在因素，并确定T细胞在疾病中的作用。将BALB/c小鼠全身致敏于卵清蛋白（OVA），并反复喂食OVA以诱导过敏性腹泻。通过定量PCR评估局部细胞因子和趋化因子的表达，并通过ELISA测定肠系膜淋巴结（MLN）中的细胞因子分泌水平。通过流式细胞术确定归巢分子的表达，并通过过继转移测试CD4(+) T细胞在促进疾病中的作用。小鼠出现腹泻，伴有上皮离子转运变化、肥大细胞浸润、肠道IgE分泌以及小肠中Th2细胞因子和Th2趋化因子CCL1、CCL17和CCL22的局部上调。在症状出现前，T细胞在MLN中被激活，单次喂食OVA可诱导T细胞增殖、α(4)β(7)上调和CD62L下调。来自MLN的细胞，包括纯化的CD4(+) T细胞，能够将过敏性腹泻转移给未致敏的小鼠。在MLN中诱导的肠道归巢表型和Th2趋化因子的选择性上调可能是食物过敏中病理性Th2偏向的CD4(+) T细胞向胃肠道募集中的重要因素。
