Department of Medicine, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm 17164, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
Cell Rep. 2019 Jul 30;28(5):1127-1135.e4. doi: 10.1016/j.celrep.2019.06.087.
Using non-human primates (NHPs), mice, and human primary cells, we found a role for interleukin-10 (IL-10) in the upregulation of the tissue-resident memory T cell (T) marker CD103. In NHPs, intravenous, but not subcutaneous, immunization with peptide antigen and an adjuvant combining an agonistic anti-CD40 antibody plus poly(IC:LC) induced high levels of CD103 Ts in the lung, which correlated with early plasma IL-10 levels. Blocking IL-10 reduced CD103 expression on human T cells stimulated in vitro with the adjuvant combination as well as diminished CD103 on lung-resident T cells in vivo in mice. Monocyte-produced IL-10 induced the release of surface-bound transforming growth factor β (TGF-β), which in turn upregulated CD103 on T cells. Early TGF-β imprinted increased sensitivity to TGF-β restimulation, indicating an early commitment of the T cell lineage toward Ts during the priming stage of activation. IL-10-mediated TGF-β signaling may therefore have a critical role in the generation of T following vaccination.
使用非人类灵长类动物（NHPs）、小鼠和人原代细胞，我们发现白细胞介素-10（IL-10）在组织驻留记忆 T 细胞（T）标志物 CD103 的上调中起作用。在 NHPs 中，静脉内而非皮下免疫肽抗原和一种佐剂（结合激动性抗 CD40 抗体和聚（IC：LC））可诱导肺中高水平的 CD103 Ts，这与早期血浆 IL-10 水平相关。阻断 IL-10 可减少体外用佐剂组合刺激的人 T 细胞上 CD103 的表达，以及减少小鼠体内肺驻留 T 细胞上 CD103 的表达。单核细胞产生的 IL-10 诱导表面结合的转化生长因子-β（TGF-β）释放，反过来又上调 T 细胞上的 CD103。早期 TGF-β 印迹增加了对 TGF-β再刺激的敏感性，表明在激活的启动阶段，T 细胞谱系向 Ts 的早期定向。因此，IL-10 介导的 TGF-β 信号通路可能在疫苗接种后 T 细胞的产生中起关键作用。
