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

Nat Immunol. 2013 Jul;14(7):741-8. doi: 10.1038/ni.2610. Epub 2013 May 19.

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. CD52(hi)CD4(+) 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 CD52(hi)CD4(+) T cells responsive to the autoantigen GAD65. In diabetes-prone mice of the nonobese diabetic (NOD) strain, transfer of lymphocyte populations depleted of CD52(hi) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD52 Antigen
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Flow Cytometry
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • Homeostasis / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Phosphorylation / immunology
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialic Acid Binding Immunoglobulin-like Lectins / immunology*
  • ZAP-70 Protein-Tyrosine Kinase / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Neoplasm
  • Autoantigens
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • RNA, Messenger
  • Sh2d2a protein, mouse
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • ZAP-70 Protein-Tyrosine Kinase