Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization.
Sublytic C5b-9 has been described as a pro-inflammatory mediator that triggers cell activation rather than inducing cell death. Dendritic cells (DC) play a critical role in controlling antigen-specific immune responses. Although DC maturation induced by various stimuli has been well characterized, the role of C5b-9 in DC function has not been described. In this report, we use in vitro assembled functional C5b-9 based on purified distal complement protein to show that DC maturation is promoted by sublytic C5b-9. This was demonstrated by up-regulation of CD83, HLA-antigens and costimulatory molecules, including CD80, D86, B7-H1, B7-H3, B7-H4 and BTLA. In addition, secretion of cytokines such as interleukin (IL)-12 and tumor necrosis factor-alpha was increased while the capacity for antigen uptake (FITC-Dextran and Lucifer Yellow) was reduced in C5b-9-treated DC. Mixed lymphocyte reactions indicated that C5b-9-activated DC acted as stimulators that significantly promoted CD4+ T cell activation and elicited production of cytokines, including interferon-gamma and IL-2. Interestingly, C5b-9-treated DC also orient CD4+ CD45RA+ naïve T cells toward Th1 polarization. Our results are the first to report that DC are potential immunoregulatory targets of C5b-9, suggesting that C5b-9 bridges innate and acquired immunity by inducing DC maturation.
Chen
Yongwen
Y
Laboratory of Immunoregulation, Institute of Immunology, PLA, The Third Military Medical University, Chongqing, P R China.
Yang
Chengying
C
Jin
Naishi
N
Xie
Zhunyi
Z
Tang
Yuyu
Y
Fei
Lei
L
Jia
Zhengcai
Z
Wu
Yuzhang
Y
D002454:Cell Differentiation / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003167:Complement Activation / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D015938:Complement Membrane Attack Complex