title: Immune complexes and late complement proteins trigger activation of Syk tyrosine kinase in human CD4(+) T cells.
abstract: In systemic lupus erythematosus (SLE), the autoantibodies that form immune complexes (ICs) trigger activation of the complement system. This results in the formation of membrane attack complex (MAC) on cell membrane and the soluble terminal complement complex (TCC). Hyperactive T cell responses are hallmark of SLE pathogenesis. How complement activation influences the T cell responses in SLE is not fully understood. We observed that aggregated human γ-globulin (AHG) bound to a subset of CD4(+)  T cells in peripheral blood mononuclear cells and this population increased in the SLE patients. Human naive CD4(+)  T cells, when treated with purified ICs and TCC, triggered recruitment of the FcRγ chain with the membrane receptor and co-localized with phosphorylated Syk. These events were also associated with aggregation of membrane rafts. Thus, results presented suggest a role for ICs and complement in the activation of Syk in CD4(+)  T cells. Thus, we propose that the shift in signalling from ζ-chain-ZAP70 to FcRγ chain-Syk observed in T cells of SLE patients is triggered by ICs and complement. These results demonstrate a link among ICs, complement activation and phosphorylation of Syk in CD4(+)  T cells.
authors.affiliation: Division of Adult and Pediatric Rheumatology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA. chauhana@slu.edu
authors.forename: A K
authors.initials: AK
authors.lastname: Chauhan
authors.forename: T L
authors.initials: TL
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000502:physiology*; D001323:Autoantibodies / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002478:Cells, Cultured / Q000201:enzymology / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology; D008297:Male; D021962:Membrane Microdomains; D008875:Middle Aged; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000502:physiology; D005719:gamma-Globulins / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015938:Complement Membrane Attack Complex; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D005719:gamma-Globulins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human