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

Jianuo Liu, Takashi Miwa, Brendan Hilliard, Youhai Chen, John D. Lambris, Andrew D. Wells, Wen Chao Song

Research output: Contribution to journalArticle

165 Citations (Scopus)

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)-γ 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-γ 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.

Original languageEnglish (US)
Pages (from-to)567-577
Number of pages11
JournalJournal of Experimental Medicine
Volume201
Issue number4
DOIs
StatePublished - Feb 21 2005

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CD55 Antigens
Immunity
Complement System Proteins
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Complement Inactivating Agents
Interferons
Interleukin-2
Glycosylphosphatidylinositols
Cancer Vaccines
Organ Transplantation
Adaptive Immunity
Interleukin-10
Disease Progression
Vaccination
Down-Regulation
Lymphocytes
Pathology
Cytokines
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Liu, J., Miwa, T., Hilliard, B., Chen, Y., Lambris, J. D., Wells, A. D., & Song, W. C. (2005). The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. Journal of Experimental Medicine, 201(4), 567-577. https://doi.org/10.1084/jem.20040863

The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. / Liu, Jianuo; Miwa, Takashi; Hilliard, Brendan; Chen, Youhai; Lambris, John D.; Wells, Andrew D.; Song, Wen Chao.

In: Journal of Experimental Medicine, Vol. 201, No. 4, 21.02.2005, p. 567-577.

Research output: Contribution to journalArticle

Liu, J, Miwa, T, Hilliard, B, Chen, Y, Lambris, JD, Wells, AD & Song, WC 2005, 'The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo', Journal of Experimental Medicine, vol. 201, no. 4, pp. 567-577. https://doi.org/10.1084/jem.20040863
Liu, Jianuo ; Miwa, Takashi ; Hilliard, Brendan ; Chen, Youhai ; Lambris, John D. ; Wells, Andrew D. ; Song, Wen Chao. / The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 4. pp. 567-577.
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