Complement receptor 3 ligation of dendritic cells suppresses their stimulatory capacity

被引:56
作者
Behrens, Edward M.
Sriram, Uma
Shivers, Debra K.
Gallucci, Marcello
Ma, Zhengyu
Finkel, Terri H.
Gallucci, Stefania
机构
[1] Childrens Hosp Philadelphia, Abramson Res Ctr 1102, Joseph Stokes Jr Res Inst,Div Rheumatol, Lab Dendrit Cell Biophys, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Pediat, Div Rheumatol, Philadelphia, PA 19104 USA
[3] Univ Milan, Fac Psychol, I-20122 Milan, Italy
关键词
D O I
10.4049/jimmunol.178.10.6268
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To activate T cells effectively, dendritic cells (DCs) must provide three separate signals, MHC-Ag, costimulatory molecules (such as CD80 and CD86), and proinflammatory cytokines (such as IL-12). These three signals are up-regulated in the presence of "danger signals" such as LPS or viral nucleic acids. Evidence suggests that DCs providing only the first two of these signals cannot successfully stimulate T cells. Apoptotic cells have been proposed to suppress DC immunogenicity through the ligation of apoptotic cell receptors. Complement receptor 3 (CR3) and CD36 have been suggested to be important in this process, although the mechanism by which this modulation occurs is still unclear. We demonstrate that ligation of CR3, but not CD36, directs DCs to increase surface MHC and costimulatory molecules, while suppressing inflammatory cytokine release. CR3 modulation of DCs does not require a type I IFN response, does not involve the specific regulation of the MyD88- or Toll/IL-1R domain-containing adaptor-inducing IFN-beta-dependent TLR signaling pathways, and occurs even in the absence of danger signals. The functional outcome of this process is poor Ag-specific stimulation of CD4 and CD8 T cells by CR3-ligated DCs both in naive response as well as upon subsequent challenge with normal DCs. We propose that CR3 provides a "nondanger" signal that suppresses the stimulatory capacity of DCs.
引用
收藏
页码:6268 / 6279
页数:12
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