title: T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10.
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.
authors.affiliation: Walter & Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Esther
authors.initials: E
authors.lastname: Bandala-Sanchez
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Simone
authors.initials: S
authors.lastname: Reinwald
authors.forename: James A
authors.initials: JA
authors.lastname: Dromey
authors.forename: Bo-Han
authors.initials: BH
authors.lastname: Lee
authors.forename: Junyan
authors.initials: J
authors.lastname: Qian
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Böhmer
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000074301:CD52 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010766:Phosphorylation / Q000276:immunology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001324:Autoantigens; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D012333:RNA, Messenger; C402726:Sh2d2a protein, mouse; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D051746:ZAP-70 Protein-Tyrosine Kinase