PDF(Pubmed)
Abstract：
Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1+ Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39+ Treg and the lower frequency of integrinα4β1+ Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.
摘要：
调节性T细胞（Treg）在子宫内耐受非遗传母体抗原和调节出生时针对病原体的免疫应答中起着重要作用。这项研究调查了西非新生儿的Treg免疫，败血症仍然是一个主要的公共卫生问题。新生儿早发性败血症（EOS）亚组的Treg表型，假定脓毒症,并对有无产前危险因素的健康新生儿进行评估。Treg表型根据产前条件而变化，与无产前危险因素的健康新生儿相比，Treg频率和Foxp3表达增加。与有产前危险因素的健康新生儿相比，EOS新生儿Treg和Foxp3表达频率显著降低。在Treg池里,在EOS新生儿中观察到更高的活化Treg频率，提示败血症发作上游的子宫内激活。它们向感染部位的迁移可以解释循环整合素α4β1+Treg的频率降低,提示归巢至内皮组织。新生儿EOS显示Treg上CTLA-4，PD-1和CD39的表达增加，其负调节效应T细胞（Teff）的激活，这由EOS新生儿中Teff的较低频率证实。EOS非存活者中CD39+Treg的频率较高，整合素α4β1+Treg的频率较低，提示Treg耗尽和内皮归巢与结果严重程度相关。发展EOS的新生儿天生具有改变的Treg表型特征。CTLA-4、PD-1、CD39和整合素α4β1细胞标志物的Treg表达可被认为是EOS的早期预警或诊断标志物。
