title: Decay-accelerating factor modulates induction of T cell immunity.
abstract: Decay-accelerating factor (Daf) dissociates C3/C5 convertases that assemble on host cells and thereby prevents complement activation on their surfaces. We demonstrate that during primary T cell activation, the absence of Daf on antigen-presenting cells (APCs) and on T cells enhances T cell proliferation and augments the induced frequency of effector cells. The effect is factor D- and, at least in part, C5-dependent, indicating that local alternative pathway activation is essential. We show that cognate T cell-APC interactions are accompanied by rapid production of alternative pathway components and down-regulation of Daf expression. The findings argue that local alternative pathway activation and surface Daf protein function respectively as a costimulator and a negative modulator of T cell immunity and explain previously reported observations linking complement to T cell function. The results could have broad therapeutic implications for disorders in which T cell immunity is important.
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lalli
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Anna
authors.initials: A
authors.lastname: Valujskikh
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.forename: Nasima
authors.initials: N
authors.lastname: Muqim
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.forename: M Edward
authors.initials: ME
authors.lastname: Medof
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D050577:Complement C3-C5 Convertases / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D015850:Interleukin-6 / Q000276:immunology; D053605:Leukemia Inhibitory Factor; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018958:CD55 Antigens; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases