title: Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response.
abstract: To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-beta and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Bernd
authors.initials: B
authors.lastname: Schröppel
authors.forename: Girdhari
authors.initials: G
authors.lastname: Lal
authors.forename: Claudia
authors.initials: C
authors.lastname: Jakubzick
authors.forename: Xia
authors.initials: X
authors.lastname: Mao
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Yin
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
authors.forename: Jordi C
authors.initials: JC
authors.lastname: Ochando
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Ding
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bromberg
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D007249:Inflammation; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*