Tissue Resident CD8+T-cells as mediators of protective immunity in breastmilk transmission of HCMV

Shara Legg, David C Moylan, Neema Kamau, Misty P Latting, Dhruv Devdhara, Sunil K Pati, David K Crossman, Suresh B Boppana, Olaf Kutsch, Steffanie Sabbaj
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Abstract

While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk. In addition, we describe tissue resident memory T-cells (Trm) in breastmilk and demonstrate most were Tem. We present data that non-transmitter moms have increased frequency of CD8+ Trm T-cells in their breastmilk when compared to transmitters and that Trm frequency is inversely correlated with breastmilk HCMV VL. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in non-transmitters and demonstrate that these cells comprise CD8+ Trm T-cells. These studies suggest that CD8+ Trm T-cells may play a role in preventing viral transmission via breastmilk to infants.
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组织驻留CD8+ t细胞在HCMV母乳传播中的保护性免疫介质作用
虽然母乳抗体保护婴儿免受巨细胞病毒感染的作用已经被研究过,但t细胞的作用却很少受到关注。我们比较了母乳中获得HCMV(递质)婴儿的母亲和未感染婴儿的母亲(非递质)母乳中记忆t细胞群的频率。非传递者母亲的母乳中CD8+效应记忆t细胞(Tem)的频率增加。此外,我们描述了母乳中的组织常驻记忆t细胞(Trm),并证明大多数是Tem。我们提供的数据表明,与传递者相比,非传递者母亲的母乳中CD8+ Trm t细胞的频率增加,并且Trm频率与母乳HCMV VL呈负相关。最后,使用scRNA-seq分析,我们在非递质中鉴定了一个独特的t细胞群,并证明这些细胞包括CD8+ Trm t细胞。这些研究表明,CD8+ Trm t细胞可能在防止病毒通过母乳传播给婴儿方面发挥作用。
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