Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
World Health Organization Collaborating Center for Vaccine Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Front Immunol. 2019 Jul 18;10:1650. doi: 10.3389/fimmu.2019.01650. eCollection 2019.
Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing "imprinting" signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare -activated Ag DCs in the lung and muscle-draining LNs. Higher frequencies of Ag CD11b DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag CD11b MedLN DCs were qualitatively superior at priming CD4 T cells, which then expressed CD49a and CXCR3, and preferentially trafficked into the lung parenchyma. CD11b DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag DCs, and DC molecule signatures are factors that can influence the output and differentiation of lung-homing CD4 T cells.
引流肠道和皮肤的树突状细胞（DC）通过向淋巴结（LN）中的 T 细胞提供“印迹”信号，有利于建立归巢到 DC-抗原（Ag）最初接触部位的 T 细胞群体。为了研究肺 T 细胞迁移的诱导，我们使用蛋白佐剂的小鼠鼻内和肌肉内免疫接种模型，比较了肺和肌肉引流淋巴结（LN）中的活化 Ag DC。与肌肉引流的腹股沟 LN（ILN）相比，引流到肺的纵隔 LN（MedLN）中观察到更高频率的 Ag CD11b DC。Ag CD11b MedLN DC 在刺激 CD4 T 细胞方面具有更好的质量，然后这些细胞表达 CD49a 和 CXCR3，并优先迁移到肺实质中。来自 MedLN 的 CD11b DC 表达更高水平的表面 podoplanin、Trem4、GL7 以及已知的共刺激分子 CD80、CD86 和 CD24。阻断特定的 MedLN DC 分子或使用分选的 DC 和 T 细胞共培养表明，DC 表面表型影响能够归巢到肺部的 T 细胞的激活能力。因此，dLN Ag DC 的密度和 DC 分子特征是影响肺归巢 CD4 T 细胞输出和分化的因素。
