Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein
Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein
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DOI：
10.1016/j.jaci.2008.09.051
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发表时间：
2009-01-01
影响因子：
14.2
通讯作者：
Sampson, Hugh A.
中科院分区：
文献类型：
--
作者：
Shreffler, Wayne G.;Wanich, Niya;Sampson, Hugh A.
背景资料：大约70%的牛奶过敏的儿童耐受广泛加热的牛奶（HM）产品和outgrow他们的过敏早于那些谁反应到HM.Objective：为了检验假设HM耐受的儿童有较高的前体频率的适应性过敏原特异性调节T细胞（Treg）cells.Methods：过敏，HM耐受，长大，或控制科目被定义为口服食物挑战。将PBMC与纯化的酪蛋白和对照一起培养7天，并通过流式细胞术鉴定增殖的CD 25（+）CD 27（+）Treg细胞。还表征了增殖细胞的FoxP 3、CTLA 4、CD 45 RO和CD 127的表达。通过培养前去除CD 25（hi）细胞来评估过敏原特异性Treg细胞的来源和功能。（中位数[25th%至75th%]，16.85% [7.1-31.7]）来自HM耐受受试者（n = 18）培养物的增殖变应原特异性CD 25（+）CD 27（+）T细胞比过敏受试者（n = 18）的增殖变应原特异性CD 25（+）CD 27（+）T细胞（n = 8; 4.91% [2.6-7.5]; P < .01）。无牛奶过敏史的对照受试者（n = 7）的这些细胞百分比也较低（2.9% [2.4-6.0]），而发育过度受试者（n = 7）的百分比居中（9.0% [2.7-16.4]）。在多克隆Treg细胞或过敏原特异性效应T细胞的频率方面，患者组之间没有显著差异。发现过敏原特异性Treg细胞是FoxP 3（+）CD 25（hi）CD 27（+）、细胞毒性T淋巴细胞相关抗原4（+）、CD 45 RO（+）CD 127（-），并且来源于循环CD 25（hi）T细胞。体外培养前CD 25（hi）细胞的耗竭显著增强了变应原特异性效应T细胞的扩增。结论：较高频率的牛奶变应原特异性Treg细胞与轻度临床疾病的表型和良好的预后相关。（J Allergy Clin Immunol 2009;123：43-52.）
Background: About 70% of children with milk allergy tolerate extensively heated milk (HM) products and outgrow their allergy earlier than those who react to HM.Objective: To test the hypothesis that HM-tolerant children have a higher precursor frequency of adaptive allergen-specific regulatory T (Treg) cells.Methods: Allergic, HM-tolerant, outgrown, or control subjects were defined by oral food challenge. PBMCs were cultured with purified caseins and controls for 7 days, and proliferating CD25(+)CD27(+) Treg cells were identified by How cytometry. Proliferating cells were also characterized for their expression of FoxP3, CTLA 4, CD45RO, and CD127. Allergen-specific Treg cell origin and function were assessed by depletion of CD25(hi) cells before culture.Results: There was a higher percentage (median [25th% to 75th%], 16.85% [7.1-31.7]) of proliferating allergen-specific CD25(+)CD27(+) T cells from cultures of HM-tolerant subjects (n = 18) than subjects with allergy (n = 8; 4.91% [2.6-7.5]; P < .01). Control subjects with no history of milk allergy (n = 7) also had low percentages of these cells (2.9% [2.4-6.0]), whereas outgrown subjects (n = 7) had intermediate percentages (9.0% [2.7-16.4]). There were no significant differences between the patient groups in the frequency of polyclonal Treg cells or allergen-specific effector T cells. Allergen-specific Treg cells were found to be FoxP3(+)CD25(hi)CD27(+), cytotoxic T lymphocyte-associated antigen 4(+), CD45RO(+)CD127(-) and were derived from circulating CD25(hi) T cells. Depletion of the CD25(hi) cells before in vitro culture significantly enhanced allergen-specific effector T-cell expansion.Conclusion: A higher frequency of milk allergen-specific Treg cells correlates with a phenotype of mild clinical disease and favorable prognosis. (J Allergy Clin Immunol 2009;123:43-52.)