apc activation restores functional cd4+cd25+ regulatory t cells in nod mice that can prevent diabetes developmentapc激活恢复功能cd4 + cd25 +调节性t细胞在小鼠点头,可以预防糖尿病的发展.pdf

+ + APC Activation Restores Functional CD4 CD25 Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development 1,2 1 1 1 Jean N. Manirarora , Michele M. Kosiewicz , Sarah A. Parnell , Pascale Alard * 1 Department of Microbiology and Immunology, University of Louisville, Health Sciences Center (HSC), Louisville, Kentucky, United States of America, 2 Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America Abstract Background: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4+CD25+ regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4+CD25+ regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. Methodology/Principal Findings: To test these hypotheses, we used the well-documented ability of complete Freund’s adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4+CD25+ regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4+CD25+ cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD c