The Journal of Experimental Medicine
Randox
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Published online 14 February 2005 doi:10.1084/jem.20040863
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 4, 567-577
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ARTICLE

 The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo

Jianuo Liu1, Takashi Miwa1, Brendan Hilliard2, Youhai Chen2, John D. Lambris2, Andrew D. Wells2,3, and Wen-Chao Song1

1 Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
3 Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

CORRESPONDENCE Wen-Chao Song: Song{at}spirit.gcrc.upenn.edu

Decay-accelerating factor ([DAF] CD55) is a glycosylphosphatidylinositol-anchored membrane inhibitor of complement with broad clinical relevance. Here, we establish an additional and unexpected role for DAF in the suppression of adaptive immune responses in vivo. In both C57BL/6 and BALB/c mice, deficiency of the Daf1 gene, which encodes the murine homologue of human DAF, significantly enhanced T cell responses to active immunization. This phenotype was characterized by hypersecretion of interferon (IFN)-{gamma} and interleukin (IL)-2, as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro. Compared with wild-type mice, Daf1–/– mice also displayed markedly exacerbated disease progression and pathology in a T cell–dependent experimental autoimmune encephalomyelitis (EAE) model. However, disabling the complement system in Daf1–/– mice normalized T cell secretion of IFN-{gamma} and IL-2 and attenuated disease severity in the EAE model. These findings establish a critical link between complement and T cell immunity and have implications for the role of DAF and complement in organ transplantation, tumor evasion, and vaccine development.

Abbreviations used: DAF, decay-accelerating factor; EAE, experimental autoimmune encephalomyelitis; GPI, glycosylphosphatidylinositol; GVBS, gelatin veronal-buffered saline; MOG, myelin oligodendrocyte glycoprotein; SEB, Staphylococcus enterotoxin B; T reg cell, T regulatory cell.


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