title: Lymph node trafficking of regulatory T cells is prerequisite for immune suppression.
abstract: Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad inflammation. In addition, although blockage of CCR7 or CD62L had no effect on the immune suppressive function of the regulatory T cells per se, pretreatment of the regulatory T cells with either CCR7 or CD62L blocking antibodies prevented their recruitment into draining lymph nodes and concomitantly abrogated the immune suppressive effects of adoptively transferred regulatory T cells during footpad inflammation. Our data demonstrate the crucial role of lymph node localization in regulatory T cell-mediated immune suppression and suggest a probable hierarchy in the anatomic sites for optimal immune regulation. Elucidating the relationships between the transmigration characteristics of the regulatory T cells and their immune regulation function will provide insightful information for regulatory T cell-based cell therapy.
authors.affiliation: Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan mthuang@ntu.edu.tw gicmbor@ntu.edu.tw.
authors.forename: Miao-Tzu
authors.initials: MT
authors.lastname: Huang
authors.affiliation: Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Been-Ren
authors.initials: BR
authors.lastname: Lin
authors.affiliation: Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Liu
authors.affiliation: Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lu
authors.affiliation: Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan mthuang@ntu.edu.tw gicmbor@ntu.edu.tw.
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D007108:Immune Tolerance; D007249:Inflammation; D019041:L-Selectin / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019041:L-Selectin
keywords: CCR7; footpad inflammation; immune regulation; leukocyte trafficking