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.
Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
%0 Journal Article
%1 Liu:2005bf
%A Liu, Jianuo
%A Miwa, Takashi
%A Hilliard, Brendan
%A Chen, Youhai
%A Lambris, John D.
%A Wells, Andrew D
%A Song, Wen-Chao
%D 2005
%J The Journal of experimental medicine
%K imported
%N 4
%P 567--577
%R 10.1084/jem.20040863
%T The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo.
%U http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=15710649&retmode=ref&cmd=prlinks
%V 201
%X 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.
@article{Liu:2005bf,
abstract = {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.},
added-at = {2017-12-08T05:18:19.000+0100},
affiliation = {Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.},
author = {Liu, Jianuo and Miwa, Takashi and Hilliard, Brendan and Chen, Youhai and Lambris, John D. and Wells, Andrew D and Song, Wen-Chao},
biburl = {https://www.bibsonomy.org/bibtex/2f4d2292548cfbd7951b681aeb7b2a3e4/lambris},
date-added = {2012-03-27T20:49:03GMT},
date-modified = {2017-12-08T04:17:04GMT},
doi = {10.1084/jem.20040863},
interhash = {cf6c9d56714d4a72ddca25e11f6da832},
intrahash = {f4d2292548cfbd7951b681aeb7b2a3e4},
journal = {The Journal of experimental medicine},
keywords = {imported},
language = {English},
month = feb,
number = 4,
pages = {567--577},
pmcid = {PMC2213052},
pmid = {15710649},
rating = {0},
timestamp = {2017-12-08T05:18:19.000+0100},
title = {{The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo.}},
uri = {\url{papers3://publication/doi/10.1084/jem.20040863}},
url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=15710649&retmode=ref&cmd=prlinks},
volume = 201,
year = 2005
}