Telethon Institute for Child Health Research and Centre for Child Health Research, School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
Immunol Cell Biol. 2010 Aug;88(6):658-66. doi: 10.1038/icb.2010.18. Epub 2010 Mar 2.
Inhaled allergens are known for their immediate and ongoing effects in the respiratory tract (RT). In this report, we track inhaled antigen in normal mice for 7 days and find that while it is cleared from the airways, inhaled antigen persists in peripheral lung tissue and the draining lymph nodes (DLNs). The persistence of antigen led to ongoing presentation in the lymph nodes, but not the lungs, that decreased with time in direct proportion with the frequency of antigen-bearing RT dendritic cells (DCs). There was evidence of functional changes among the antigen-bearing DCs in the lymph nodes, as the expression of CD40, CD80 and CD86 were modulated over the course of 7 days. At the same time, there was a decrease in both CD4(+) T-cell proliferation in lymph nodes and the generation of recirculating CD4(+) T cells. However, early presentation of lower doses of inhaled antigen also resulted in a decrease in CD4(+) T-cell proliferation and recirculation. Thus, T-cell recirculation depends on the strength of stimulus in the DLNs and is produced by a combination of the dose of antigen delivered to the RT, DC migration and co-stimulatory molecule expression. These results provide an important insight into the fate of inhaled antigen in vivo and the influence of persistent antigen presentation on T-cell activation in the lymph nodes.
吸入性过敏原已知对呼吸道 (RT) 具有即时和持续的影响。在本报告中，我们在正常小鼠中追踪吸入的抗原 7 天，发现尽管它已从气道中清除，但仍存在于外周肺组织和引流淋巴结 (DLN) 中。抗原的持续存在导致在淋巴结中持续呈递，但不在肺部呈递，随着时间的推移，与携带抗原的 RT 树突状细胞 (DC) 的频率成比例地减少。在淋巴结中携带抗原的 DC 中存在功能变化的证据，因为 CD40、CD80 和 CD86 的表达在 7 天的过程中被调节。与此同时，淋巴结中 CD4(+) T 细胞增殖和循环 CD4(+) T 细胞的产生减少。然而，较低剂量吸入性抗原的早期呈递也导致 CD4(+) T 细胞增殖和再循环减少。因此，T 细胞再循环取决于 DLN 中刺激的强度，并由输送到 RT 的抗原剂量、DC 迁移和共刺激分子表达的组合产生。这些结果提供了对体内吸入性抗原命运以及持续抗原呈递对淋巴结中 T 细胞活化影响的重要见解。
