Reconstruct Of Specific Immune Tolerance By Proinflammatory Factor-Mediated Over-expression Of HVEM On Peptide-loaded Dendritic Cells

This study has four parts:In the first part we constructed the luciferase reporter plasmid and adenovirus containing IL1/IL6 hybrid promoter to evaluate its inducible expression characters in vitro and in vivo. In the second part, on the basis of confirmative conclusion of inducible ability of IL1/IL6 hybrid promoter, we constructed another adenovirus which the IL1/IL6 drives HVEM expression, and transferred it into murine myeloid DCs. The physiological properties of HVEM modified DCs were analyzed. We found HVEM modified DCs resisted to mature induced by LPS, and inhibited allogenic CD4+ T cell proliferation. It also decreased secretion of proinflammatory factors. In the third part we established an experimental autoimmune myocarditis model to investigate the role of HVEM modified DCs in prevention against autoimmune lesion. HVEM modified DCs ameliorated myocarditis, inhibited autoimmune reaction and production of autoantibodies. In addition, it altered the ratio of Th subsets that the ratio of Th1 increased while that of Th17 decreased. In the fourth part we found the HVEM modified DCs regulated Tr1 reaction and prolonged the survival of Treg, which suggested the protection mechanisms of HVEM modified DCs might partly depend on induction of regulatory T cells.