Chinese Journal of Organ Transplantation 1996;0(02):-
Effect of NF-?B Decoys on development and maturation of dendritic cells and in itiation of Tcells immune response in vitro
Dongliang XU ; Xiaoda TANG ; Bo LI
Keywords
NF-?B; Oligonucleotide probes; Dendrit ic cells; Immune tolerance
Country
China
Language
Chinese
Abstract
ObjectiveTo investigate the effect of NF-?B on the differentiation and maturation of mu rine bone marrow-derived dendritic cells (DC) in vitro.MethodsThe activity of NF-?B in dendritic cells was blocked by oligodeoxyribonucleot ide Decoys (ODN Decoys) containing two special binding sites for NF-?B. Morpho logical changes of DS were observed. The expression of assistant molecules on th e cell surface was detected by using flow cytometer, and the stimulating activit y of allogeneic T lymphocyte proliferative response was determined in culture mu rine DC. The effect of NF-?B on the maturation and immunobiological activity o f murine DC was studied.ResultsNF-?B ODN Decoys were efficiently incorporated by DC, markedly suppressed the maturation of DC, the expression of assistant costimulatory molecules (CD80, CD8 6 and CD40) on the surface of DC and the secretion of IL-12, blocked the develo pment of DC and this blocked function was not reversed by lipopolysaccharide (LP S). In mixed lymphocyte reactions, DC treated with NF-?B ODN Decoys could indu ce allogeneic T cells hyphoresponsiveness, and this was associated with the inhi bition of Th1-type cytokines (IL-2 and IFN-?) production.ConclusionsNF-? B is a key gene to the development and maturation of DC. Specific interference w ith NF-?B in DC using ODN Decoys approaches could offer a novel strategy for i nducing and generating tolerogeneic immature DC and provide a promising means to induce transplant immune tolerance.
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