Sialoadhesin ligand expression identifies a subpopulation of Foxp3- T cells with a distinct activation and glycosylation profile

D Kidder, H E Richards, H J Ziltener, O A Garden, P R Crocker (Lead / 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-? 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 a2,3-sialylation in SnL expression was demonstrated by increased binding of a2,3-linkage–specific Maackia amurensis lectin, increased expression of a2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an a2,3-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
    JournalJournal of Immunology
    Volume190
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2013

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