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T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10

Nature Immunology volume 14, pages 741–748 (2013)Cite this article

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Abstract

Functionally diverse T cell populations interact to maintain homeostasis of the immune system. We found that human and mouse antigen-activated T cells with high expression of the lymphocyte surface marker CD52 suppressed other T cells. CD52hiCD4+ T cells were distinct from CD4+CD25+Foxp3+ regulatory T cells. Their suppression was mediated by soluble CD52 released by phospholipase C. Soluble CD52 bound to the inhibitory receptor Siglec-10 and impaired phosphorylation of the T cell receptor–associated kinases Lck and Zap70 and T cell activation. Humans with type 1 diabetes had a lower frequency and diminished function of CD52hiCD4+ T cells responsive to the autoantigen GAD65. In diabetes-prone mice of the nonobese diabetic (NOD) strain, transfer of lymphocyte populations depleted of CD52hi cells resulted in a substantially accelerated onset of diabetes. Our studies identify a ligand-receptor mechanism of T cell regulation that may protect humans and mice from autoimmune disease.

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Figure 1: CD52 expression distinguishes suppressor CD4+ T cells in healthy people.
Figure 2: CD52hi T cells are distinct from CD4+CD25+ Treg cells.
Figure 3: GAD65-activated CD52hi T cells are impaired in type 1 diabetes.
Figure 4: CD52hi T cells retard the development of diabetes in NOD mice.
Figure 5: Soluble CD52 mediates suppression by CD52hi T cells.
Figure 6: Soluble CD52 inhibits activation via the TCR.
Figure 7: Soluble CD52 binds via its glycan moiety to Siglec-10.

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Acknowledgements

We thank M.R. Clark (University of Cambridge) for DNA encoding immunoglobulin G1 Fc; and L. Belov, K. Ngui, A. Neale, J. Butler, D. Mittag, M. Herold, N. Stone, N. Lynch, H. Thomas, S. Finch and T. Adams for technical assistance and advice. Supported by the National Health and Medical Research Council of Australia (637301 to L.C.H. and 516700) and facilitated by the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme.

Author information

Author notes

  1. James A Dromey & Junyan Qian

    Present address: Present addresses: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Australia (D.M.B.) and Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (J.Q.).,

  2. Esther Bandala-Sanchez and Yuxia Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Walter & Eliza Hall Institute of Medical Research, Parkville, Australia

    Esther Bandala-Sanchez, Yuxia Zhang, Simone Reinwald, James A Dromey, Bo-Han Lee, Junyan Qian, Ralph M Böhmer & Leonard C Harrison

  2. Department of Medical Biology, University of Melbourne, Parkville, Australia

    Esther Bandala-Sanchez, Yuxia Zhang, Simone Reinwald, Bo-Han Lee, Junyan Qian, Ralph M Böhmer & Leonard C Harrison

  3. Burnet Clinical Research Unit, The Royal Melbourne Hospital, Parkville, Australia

    Leonard C Harrison

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Contributions

L.C.H., J.A.D., E.B.-S., Y.Z., S.R., B.-H.L., J.Q. and R.M.B. designed the studies; L.C.H. drafted the manuscript; E.B.-S., Y.Z. and R.M.B. assisted in redrafting the manuscript; and all authors did the molecular and cellular studies, analyzed the data and discussed and commented on the manuscript.

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Correspondence to Leonard C Harrison.

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Bandala-Sanchez, E., Zhang, Y., Reinwald, S. et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol 14, 741–748 (2013). https://doi.org/10.1038/ni.2610

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