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 journalArticle

18 Citations (Scopus)

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
Publication statusPublished - Dec 1 2013

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Regulatory T-Lymphocytes
Lymph Nodes
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Autoimmunity
Cell Movement
Wild Animals
P-selectin ligand protein
Autoantigens
Myelin Sheath
Photons
Confocal Microscopy
Dendritic Cells
Autoimmune Diseases
Cluster Analysis
Immunization
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Angiari, S., Rossi, B., Piccio, L., Zinselmeyer, B. H., Budui, S., Zenaro, E., ... Constantin, G. (2013). Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1. Journal of Immunology, 191(11), 5489-5500. https://doi.org/10.4049/jimmunol.1301235

Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1. / Angiari, Stefano; Rossi, Barbara; Piccio, Laura; Zinselmeyer, Bernd H.; Budui, Simona; Zenaro, Elena; Della Bianca, Vittorina; Bach, Simone D.; Scarpini, Elio; Bolomini-Vittori, Matteo; Piacentino, Gennj; Dusi, Silvia; Laudanna, Carlo; Cross, Anne H.; Miller, Mark J.; Constantin, Gabriela.

In: Journal of Immunology, Vol. 191, No. 11, 01.12.2013, p. 5489-5500.

Research output: Contribution to journalArticle

Angiari, S, Rossi, B, Piccio, L, Zinselmeyer, BH, Budui, S, Zenaro, E, Della Bianca, V, Bach, SD, Scarpini, E, Bolomini-Vittori, M, Piacentino, G, Dusi, S, Laudanna, C, Cross, AH, Miller, MJ & Constantin, G 2013, 'Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1', Journal of Immunology, vol. 191, no. 11, pp. 5489-5500. https://doi.org/10.4049/jimmunol.1301235
Angiari, Stefano ; Rossi, Barbara ; Piccio, Laura ; Zinselmeyer, Bernd H. ; Budui, Simona ; Zenaro, Elena ; Della Bianca, Vittorina ; Bach, Simone D. ; Scarpini, Elio ; Bolomini-Vittori, Matteo ; Piacentino, Gennj ; Dusi, Silvia ; Laudanna, Carlo ; Cross, Anne H. ; Miller, Mark J. ; Constantin, Gabriela. / Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1. In: Journal of Immunology. 2013 ; Vol. 191, No. 11. pp. 5489-5500.
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