Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model
作者： Yifan Ma , Louis Poisson , Guzman Sanchez-Schmitz , Santosh Pawar , Chunfeng Qu
DOI: 10.1111/J.1365-2567.2009.03237.X
关键词:
摘要: SUMMARY The in vitro Peripheral Tissue Equivalent (PTE) module is a three-dimensional tissue-engineered endothelial cell/collagen matrix culture system, which has been reported to reproduce vivo physiological conditions and generates dendritic cells (DC) autonomously. In the present study, we used PTE investigate immunopotency of Toll-like receptor (TLR) agonists, including polyinosine-polycytidylic acid, Gardiquimod, CpG 2006 lipopolysaccharide. Application TLR agonists induced wide range cytokines, interleukins 1alpha/beta, 6, 8 10 tumour necrosis factor-alpha. Compared with traditional peripheral blood mononuclear cell (PBMC) cultures, produced twofold 100-fold higher levels cytokine secretion, indicating that it can be highly sensitive assay system. This increased sensitivity result natural synergy between leucocytes endothelium. Furthermore, application such as lipopolysaccharide enhanced DC differentiation promoted maturation, indicated by up-regulated expression CD83, CD86 CCR7(CD197). addition, functional assays PTE-derived treated TLR-7 agonist, significantly augmented anti-tetanus toxoid antibody production. Interestingly, replacing PBMC purified myeloid (CD33(+)) reduced responsiveness stimulation. was partly removal plasmacytoid participated response stimulation sensitization module. Overall, clearly demonstrated effects on generation, maturation antigen-presenting capacity, may serve predictive test bed for evaluation adjuvant candidates.
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