Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1

Stefano Angiari, Barbara Rossi, Laura Piccio, Bernd H. Zinselmeyer, Simona Budui, Elena Zenaro, Vittorina Della Bianca, Simone D. Bach, Elio Scarpini, Matteo Bolomini-Vittori, Gennj Piacentino, Silvia Dusi, Carlo Laudanna, Anne H. Cross, Mark J. Miller, Gabriela Constantin

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish
Pages (from-to)5489-5500
Number of pages12
JournalJournal of Immunology
Volume191
Issue number11
DOIs
StatePublished - Dec 1 2013

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