Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Department of Physiology, Department of Microbiology and Immunology, McGill Research Centre for Complex Traits, McGill University, Montreal, QC, Canada.
Immunol Cell Biol. 2019 Oct;97(9):787-798. doi: 10.1111/imcb.12276. Epub 2019 Jun 17.
Regulatory T cells (Tregs) continuously suppress autoreactive immune responses within tissues to prevent autoimmunity, yet the recirculatory behavior of Tregs between and within tissues enabling the maintenance of peripheral tolerance remains incompletely defined. Here, we quantified homing efficiency to and the dwell time of Tregs within secondary lymphoid organs (SLOs) and used intravital two-photon microscopy to measure Treg surveillance behavior of dendritic cells. Tregs homed substantially less efficiently to SLOs compared with conventional CD4 T cells (Tconvs), despite similar expression of homing receptors. Tregs remained on average 2-3 times longer within the LN than Tconvs before exiting, and retained Tregs differed from recirculating Tregs in phenotype, motility and interaction duration with dendritic cells. Taken together, these data revealed fundamental differences in Treg versus conventional T cell in vivo recirculation and migration behaviors, identified a Treg population with prolonged LN dwell time, and provided quantitative insight into their spatiotemporal behavior within LNs.
调节性 T 细胞（Tregs）持续抑制组织内的自身反应性免疫应答，以防止自身免疫，但 Tregs 在组织间和组织内的再循环行为如何维持外周耐受仍不完全清楚。在这里，我们量化了 Tregs 归巢到次级淋巴器官（SLOs）的效率和在 SLOs 中的停留时间，并使用活体双光子显微镜测量了树突状细胞的 Treg 监测行为。与传统的 CD4 T 细胞（Tconvs）相比，Tregs 归巢到 SLOs 的效率要低得多，尽管它们表达的归巢受体相似。Tregs 在离开前平均在 LN 中的停留时间比 Tconvs 长 2-3 倍，并且离开的 Tregs 在表型、迁移能力和与树突状细胞的相互作用持续时间方面与循环 Tregs 不同。总之，这些数据揭示了 Treg 与传统 T 细胞在体内再循环和迁移行为方面的根本差异，确定了具有延长 LN 停留时间的 Treg 群体，并提供了对其在 LN 内时空行为的定量见解。
