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)

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20 Citations (Scopus)


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
Issue number6
Early online date1 Mar 2013
Publication statusPublished - 15 Mar 2013

Bibliographical note

We thank Dr. Douglas Carlow (University of British Columbia) for helpful discussions.
This work was supported by Wellcome Trust Clinical Fellowship 087078 (to D.K.) and Wellcome Trust Senior Fellowship 081882MA (to P.R.C.).


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