Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3 T Cells with a Distinct Activation and Glycosylation Profile

Dana Kidder, Hannah E. Richards, Hermann J. Ziltener, Oliver A. Garden, Paul R. Crocker (Corresponding Author)

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Sialoadhesin (Sn) is a sialic acid–binding Ig-like lectin expressed selectively on macrophage subsets. In a model of experimental autoimmune encephalomyelitis, Sn interacted with sialylated ligands expressed selectively on CD4+Foxp3+ regulatory T cells (Tregs) and inhibited their proliferation. In this study, we examined the induction of Sn ligands (SnL) on all splenic CD4+ T cells following in vitro activation. Most CD4+ Tregs strongly upregulated SnL, whereas only a small subset of ∼20% CD4+Foxp3− T cells (effector T cells [Teffs]) upregulated SnL. SnL+ Teffs displayed higher levels of activation markers CD25 and CD69, exhibited increased proliferation, and produced higher amounts of IL-2 and IFN-γ than corresponding SnL− Teffs. Coculture of activated Teffs with Sn+ macrophages or Sn+ Chinese hamster ovary cells resulted in increased cell death, suggesting a regulatory role for Sn–SnL interactions. The key importance of α2,3-sialylation in SnL expression was demonstrated by increased binding of α2,3-linkage–specific Maackia amurensis lectin, increased expression of α2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an α2,3-linkage–specific sialidase. The induction of SnL on activated CD4+ T cells was dependent on N-glycan rather than O-glycan biosynthesis and independent of the mucin-like molecules CD43 and P-selectin glycoprotein ligand-1, previously implicated in Sn interactions. Induction of ligands on CD4+Foxp3− Teffs was also observed in vivo using the New Zealand Black × New Zealand White F1 murine model of spontaneous lupus and SnL levels on Teffs correlated strongly with the degree of proteinuria. Collectively, these data indicate that SnL is a novel marker of activated CD4+ Teffs that are implicated in the pathogenesis of autoimmune diseases.
Original languageEnglish
Pages (from-to)2593-2602
Number of pages10
JournalThe Journal of Immunology
Volume190
Issue number6
Early online date1 Mar 2013
DOIs
Publication statusPublished - 15 Mar 2013

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