Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1
Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1
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DOI：
10.1182/blood-2012-06-437566
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发表时间：
2012-11-22
期刊：
影响因子：
20.3
通讯作者：
Kuijpers, Taco W.
中科院分区：
文献类型：
--
作者：
Bunders, Madeleine J.;van der Loos, Chris M.;Kuijpers, Taco W.
尽管具有潜在的临床重要性，但尚未确定HIV-1母婴传播的靶细胞。脐带血来源的CD 4（+）T细胞主要是幼稚的，不表达CCR 5，这是婴儿中传播HIV-1 R5株的强制性辅助受体。在目前的研究中，我们证明，在人类胎儿和婴儿的肠道粘膜，已经有一个大的粘膜记忆CD 4（+）CCR 5（+）T细胞的亚群，主要是一个Th 1和Th 17表型。使用下一代TCR β链测序，克隆扩增的T细胞作为记忆发育的标志在肠粘膜中占主导地位（30%），而在淋巴结中发现很少（1%），在脐带血中没有发现（0%）。肠道粘膜胎儿和婴儿CD 4（+）T细胞对HIV-1高度敏感，没有任何预刺激; pol前病毒DNA水平与感染的植物血凝素刺激的成人PBMC相似。总之，在目前的研究中，我们发现广泛的适应性免疫在出生前就存在，肠道粘膜是记忆性CD 4（+）T细胞的首选部位。婴儿粘膜中的这些CD 4（+）CCR 5（+）T细胞为出生时和母乳喂养期间摄入的HIV-1提供了大量易感细胞，表明可以在预防策略中针对母婴传播的粘膜途径。（血。2012;120（22）：4383-4390）
Despite potential clinical importance, target cells for mother-to-child transmission of HIV-1 have not yet been identified. Cord blood-derived CD4(+) T cells are largely naive and do not express CCR5, the mandatory coreceptor for transmitted HIV-1 R5 strains in infants. In the present study, we demonstrate that in the human fetal and infant gut mucosa, there is already a large subset of mucosal memory CD4(+)CCR5(+) T cells with predominantly a Th1 and Th17 phenotype. Using next-generation sequencing of the TCR beta chain, clonally expanded T cells as a hallmark for memory development predominated in the gut mucosa (30%), whereas few were found in the lymph nodes (1%) and none in cord blood (0%). The gut mucosal fetal and infant CD4(+) T cells were highly susceptible to HIV-1 without any prestimulation; pol proviral DNA levels were similar to infected phytohemagglutinin-stimulated adult PBMCs. In conclusion, in the present study, we show that extensive adaptive immunity is present before birth and the gut mucosa is the preferential site for memory CD4(+) T cells. These CD4(+)CCR5(+) T cells in the infant mucosa provide a large pool of susceptible cells for ingested HIV-1 at birth and during breastfeeding, indicating a mucosal route of mother-to-child transmission that can be targeted in prevention strategies. (Blood. 2012;120(22):4383-4390)