title: Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1.
abstract: Regulatory T cells (Tregs) maintain tolerance toward self-antigens and suppress autoimmune diseases, although the underlying molecular mechanisms are unclear. In this study, we show that mice deficient for P-selectin glycoprotein ligand-1 (PSGL-1) develop a more severe form of experimental autoimmune encephalomyelitis than wild type animals do, suggesting that PSGL-1 has a role in the negative regulation of autoimmunity. We found that Tregs lacking PSGL-1 were unable to suppress experimental autoimmune encephalomyelitis and failed to inhibit T cell proliferation in vivo in the lymph nodes. Using two-photon laser-scanning microscopy in the lymph node, we found that PSGL-1 expression on Tregs had no role in the suppression of early T cell priming after immunization with Ag. Instead, PSGL-1-deficient Tregs lost the ability to modulate T cell movement and failed to inhibit the T cell-dendritic cell contacts and T cell clustering essential for sustained T cell activation during the late phase of the immune response. Notably, PSGL-1 expression on myelin-specific effector T cells had no role in T cell locomotion in the lymph node. Our data show that PSGL-1 represents a previously unknown, phase-specific mechanism for Treg-mediated suppression of the persistence of immune responses and autoimmunity induction.
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy;
authors.forename: Stefano
authors.initials: S
authors.lastname: Angiari
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Zinselmeyer
authors.forename: Simona
authors.initials: S
authors.lastname: Budui
authors.forename: Elena
authors.initials: E
authors.lastname: Zenaro
authors.forename: Vittorina
authors.initials: V
authors.lastname: Della Bianca
authors.forename: Simone D
authors.initials: SD
authors.lastname: Bach
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Matteo
authors.initials: M
authors.lastname: Bolomini-Vittori
authors.forename: Gennj
authors.initials: G
authors.lastname: Piacentino
authors.forename: Silvia
authors.initials: S
authors.lastname: Dusi
authors.forename: Carlo
authors.initials: C
authors.lastname: Laudanna
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein