Endogenous Expression of the Human CD83 Attenuates EAE Symptoms in Humanized Transgenic Mice and Increases the Activity of Regulatory T Cells.

摘要: The CD83 is a type I membrane protein and part of the immunoglobulin superfamily receptors. involved in regulation antigen presentation dendritic cell dependent allogeneic T proliferation. A soluble form inhibits maturation function. Furthermore, expressed on activated B cells, particular regulatory cells. Previous studies murine demonstrated this molecule to be several immune-regulatory processes, comprising that plays key role development und function different immune In order get further insights into human provide preclinical tools guide CD83/sCD83 for therapeutic purposes we generated Bacterial Artificial Chromosomes (BAC) transgenic mice. BACs are excellent manipulating large DNA fragments utilized engineer mice by pronuclear injection. Two founders BAC expressing (BAC-hCD83tg mice) were examined hCD83 expression cells as well both vitro vivo (hCD83) health disease. Here, found present DCs, subtypes CD4+ CD8+ other hand, showed almost no expression. To address hCD83, performed mixed lymphocyte reactions (MLR) suppression assays used model experimental autoimmune encephalomyelitis (EAE) comparing wild-type hCD83-BAC Results herein clearly diminished capacity hCD83-BAC-derived proliferate accompanied an enhanced activation suppressive activity Tregs. recover faster from EAE-associated symptoms than mice, encouraging relevance also phenotype Tregs vivo.