In utero priming of allergen-specific helper T cells
In utero priming of allergen-specific helper T cells
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DOI：
10.1046/j.1365-2222.2001.01215.x
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发表时间：
2001-11-01
影响因子：
6.1
通讯作者：
Barker, RN
中科院分区：
文献类型：
--
作者：
Devereux, G;Seaton, A;Barker, RN
变态反应性疾病是发达国家的主要健康问题。出生时的脐带血单核细胞（CBMC）可以在过敏原刺激后增殖，这导致了广泛的观点，即过敏原对胎儿免疫系统的致敏是建立对过敏的免疫偏见的关键决定因素。然而，免疫系统可以在子宫内由过敏原启动的观点仍未得到证实。测定应答T辅助细胞的CD45亚型是确定应答T辅助细胞激活状态的既定方法，因为未致敏细胞表达CD45RA（高），而先前致敏细胞表达CD45RO（高）。目的通过检测CBMC对过敏原反应增殖的CD45亚型，确定子宫内是否会发生过敏原特异性T辅助细胞的致敏。方法用变应原、有丝分裂原和对照抗原刺激培养后，观察CBMC的增殖反应。为了确定是否有任何应答的T辅助细胞在子宫内被启动，耗尽实验确定它们是否携带CD45RO（高）先前激活的标记或CD45RA（高）未刺激T细胞的标记。结果223例随机选取的新生儿CBMC在体外受过敏原刺激增殖，其中76%的新生儿对timothygrass花粉有应答。在50%的对提莫草的反应中，增殖的T细胞的CD45异构体表明它们之前被激活过。然而，其余50%的对蒂莫西草的反应是由先前未刺激的T细胞介导的。子宫内致敏CBMC介导的增殖反应比未致敏细胞介导的增殖反应更大（P=0.08）。75%的CBMC样本在PPD分枝杆菌刺激后增殖，与接种过bcg的成年人一样，出生时所有这些CBMC增殖反应主要由致敏细胞介导。结论致敏原特异性和抗原特异性Th细胞可在子宫内启动。
Background Allergic diseases are major health problems in developed countries. Cord blood mononuclear cells (CBMC) at birth can proliferate after stimulation with allergen and this has led to the widespread view that the sensitization of the fetal immune system by allergens is a key determinant in establishing immunological bias towards allergy. However, the notion that the immune system can be primed by allergen in utero remains unproven. Determination of the CD45 isoform of responding T helper cells is an established method of determining the activation status of responding T helper cells because unsensitized cells express CD45RA(high) and previously sensitized cells CD45RO(high).Objective To determine if sensitization of allergen-specific T helper cells can occur in utero by determining the CD45 isoform of CBMC proliferating in response to allergen.Methods CBMC proliferative responses were measured after stimulation in culture with a panel of allergens, mitogen and control antigen. To ascertain whether any responding T helper cells had been primed in utero, depletion experiments established whether they carried the CD45RO(high) marker of previous activation or the CD45RA(high) marker of unstimulated T cells.Results CBMC from a high proportion of 223 randomly selected neonates were stimulated to proliferate in vitro by allergens, with 76% responding to timothy grass pollen. In 50% of such responses to timothy grass, the CD45 isoform of the T cells that proliferate indicated that they had been previously activated. However, the remaining 50% of responses to timothy grass were mediated by previously unstimulated T cells. Proliferative responses mediated by CBMC sensitized in utero tended to be greater in magnitude than those mediated by unsensitized cells (P=0.08). Seventy-five per cent of CBMC samples proliferated after stimulation with mycobacterial PPD and, as in BCG-vaccinated adults, all such CBMC proliferative responses at birth were predominately mediated by sensitized cells.Conclusion Allergen- and antigen-specific Th cells can be primed in utero.