Decay-accelerating factor modulates induction of T cell immunity.
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.
Heeger
Peter S
PS
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Lalli
Peter N
PN
Lin
Feng
F
Valujskikh
Anna
A
Liu
Jinbo
J
Muqim
Nasima
N
Xu
Yuanyuan
Y
Medof
M Edward
ME
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*
D018958:CD55 Antigens; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases