Lymph node trafficking of regulatory T cells is prerequisite for immune suppression. Issue 4 (5th November 2015)

• Record Type: Journal Article
• Authors: Huang, Miao‐Tzu; Lin, Been‐Ren; Liu, Wei‐Liang; Lu, Chun‐Wei; Chiang, Bor‐Luen
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 4(2016)
• Page Start: 561
• Page End: 568
• Publication Date: 2015-11-05
• Subjects: CCR7 -- leukocyte trafficking -- immune regulation -- footpad inflammation; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1A0715-296R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Abrogation of Treg‐mediated immunosuppression by blockage of Treg LN trafficking suggests a hierarchy of the anatomic sites for immune regulation in Treg‐based cell therapy. 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.