down regulation of genes involved in t cell polarity and motility during the induction of heart allograft tolerance by allochimeric mhc i基因参与调节t细胞极性和运动性心脏同种异体移植物耐受的诱导期间allochimeric mhc i.pdfVIP

Down Regulation of Genes Involved in T Cell Polarity and Motility during the Induction of Heart Allograft Tolerance by Allochimeric MHC I 1 2 2 2 2 Wojciech Lisik , Neelam Tejpal , Yongquan Gong , T. Spencer Skelton , Malathesh Ganachari , 3 2 2 Eric G. Bremer , Malgorzata Kloc *, Rafik M. Ghobrial * 1 Department of General and Transplantation Surgery, Warsaw Medical University, Warsaw, Poland, 2 The Methodist Hospital and The Methodist Hospital Research Institute, Houston, Texas, United States of America, 3 Precision Biomarker Resources, Inc, Evanston, Illinois, United States of America Abstract Background: The allochimeric MHC class I molecule [a1h1/u]-RT1.Aa that contains donor-type (Wistar Furth, WF; RT1u) epitopes displayed on recipient-type (ACI, RT1a) administered in conjunction with sub-therapeutic dose of cyclosporine (CsA) induces indefinite survival of heterotopic cardiac allografts in rat model. In vascularized transplantation models, the spleen contributes to graft rejection by generating alloantigen reactive T cells. The immune response in allograft rejection involves a cascade of molecular events leading to the formation of immunological synapses between T cells and the antigen-presenting cells. Methodology/Principal Findings: To elucidate the molecular pathways involved in the immunosuppressive function of allochimeric molecule we performed microarray and quantitative RTPCR analyses of gene expression profile of splenic T cells from untreated, CsA treated, and allochimeric molecule + subtherapeutic dose of CsA treated animals at day 1, 3 and 7 of post transplantation. Allochimeric