Decay-accelerating factor modulates induction of T cell immunity

• DOI: 10.1084/jem.20041967
• Publication Date: 2005-05-10T00:24:12Z
• Authors: Peter S. Heeger; Peter N. Lalli; Feng Lin; Anna Valujskikh; Jinbo Liu; Nasima Muqim; Yuanyuan Xu; M. Edward Medof
• Keywords: Male; Mice, Knockout; Immunity, Cellular; CD55 Antigens; Interleukin-6; T-Lymphocytes; Brief Definitive Report; Down-Regulation; Cell Communication; Complement C3-C5 Convertases; Complement System Proteins; Dendritic Cells; Lymphocyte Activation; Leukemia Inhibitory Factor; Enzyme Activation; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Female; Cell Proliferation; Signal Transduction

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.