title: T cell activation by terminal complex of complement and immune complexes.
abstract: T cell hyperactivation and complement consumption are prominent features of the immunopathology of systemic lupus erythematosus. Although complement activation is secondary to autoantibodies that form immune complexes (ICs), the trigger for alterations in human peripheral blood T cells is poorly understood. To study the impact (on T cells) of several types of preformed ICs and terminal complement complex, also referred to as C5b-9, we incubated these immune reactants with peripheral blood naive CD4(+) T cells as well as Jurkat cells and analyzed their effects on cellular behavior. We first assembled the C5b-9 in situ on the membrane and observed its assembly primarily on a single site where it promoted aggregation of membrane rafts and recruitment of the CD3 signaling complex. However, C5b-9 alone did not initiate proliferation or commencement of downstream signaling events associated with T cell activation. When T cells were treated with ICs together with nonlytic C5b-9, changes associated with T cell activation by possible antigen engagement then occurred. T cell antigen receptor signaling proteins, including ζ-chain, ZAP-70, Syk, Src, and Lck, were phosphorylated and organized in a synapse-like structure. The cytoskeleton formed F-actin spindles and a distal pole complex, resulting in a bipolar distribution of phosphorylated ezrin-radixin-moesin and F-actin. Furthermore, ICs and nonlytic C5b-9 induced T cell proliferation and IFN-γ production. These results raise the possibility that ICs and the nonlytic C5b-9 modulate T cell-mediated responses in systemic lupus erythematosus and other related chronic inflammatory disorders.
authors: Division of Adult and Pediatric Rheumatology, Saint Louis University School of Medicine, St. Louis, Missouri 63104. Electronic address: chauhana@slu.edu.
authors: Anil K
authors: AK
authors: Chauhan
authors: Division of Adult and Pediatric Rheumatology, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
authors: Terry L
authors: TL
authors: Moore
mesh_terms: D000199:Actins / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000737:chemistry*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D025581:Neurofibromin 2 / Q000737:chemistry; D010047:Ovalbumin / Q000737:chemistry; D010766:Phosphorylation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D000199:Actins; D017252:CD3 Complex; D015938:Complement Membrane Attack Complex; D025581:Neurofibromin 2; D007371:Interferon-gamma; D010047:Ovalbumin; D003165:Complement System Proteins