The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo.
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.
Liu
Jianuo
J
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Miwa
Takashi
T
Hilliard
Brendan
B
Chen
Youhai
Y
Lambris
John D
JD
Wells
Andrew D
AD
Song
Wen-Chao
WC
D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018958:CD55 Antigens; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma; D003165:Complement System Proteins