Alternatively Expressed Genes Identified in the CD4⁺ T Cells of Allograft Rejection Mice

Abstract

Allograft rejection is a leading cause for the failure of allotransplantation. CD4+ T cells play critical roles in this process. The identification of genes that alternatively expressed in CD4 + T cells during allograft rejection will provide critical information for studying the mechanism of allograft rejection, finding specific gene markers for monitoring, predicting allograft rejection, and opening new ways to regulate and prevent allograft rejection. Here, we established allograft and isograft transplantation models by adoptively transferring wild-type BALB/c mouse CD4+ T cells into severe combined immunodeficient (SCID) mice with a C57BL/ 6 or BALB/c mouse skin graft. Using the whole transcriptome sequencing-based serial analysis of gene expression (SAGE) technology, we identified 97 increasingly and 88 decreasingly expressed genes that may play important roles in allograft rejection and tolerance. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance, and signal transduction are among the frequently changed functional groups. This study provides a genome-wide view for the candidate genes of CD4 + T cells related to allotransplantation, and this report is a good resource for further microarray studies and for identifying the specific markers that are associated with clinical organ transplantations.

Persistence of Gene Expression Profile in CD200 Transgenic Skin Allografts Is Associated With Graft Survival on Retransplantation to Normal Recipients

“…2B). Xu et al (10) recently reported a gene expression profile comparison after isoskin or alloskin grafting into severe combined immunodeficient mice with homologous T-cell transfer as a means to obtain a genome-wide view for candidate genes in CD4 + T cells related to allotransplantation. The data in our study compared intragraft mRNA profiles in grafts transplanted into primary or secondary recipients and highlight a role for genes associated with Tregs, already implicated in the acceptance of primary grafts under cover of CD200 overexpression (6), in the maintenance of graft survival, and immunomodulation, in secondary recipients.…”

“…In all our studies of CD200-mediated immunoregulation, we have explored immunity and gene expression profiles in primary recipients where the CD200/CD200R immunoregulatory axis was perturbed. Other groups have similarly focused on characterization of the gene expression profile in primary graft recipients (9,10). Increased attention is now directed at mechanism(s) responsible for ongoing attenuation of rejection.…”

IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection

“…Our previous study indicated that IL-27Rα was up-regulated in CD4 + T cells in acute allorejection [16]. Meanwhile, we also demonstrated that increased IL-27Rα expression promoted alloreactive spleen cell proliferation.…”

“…Our previous study proved that IL-27Rα was up-regulated in CD4 + T cell-mediated allorejection. Data reported that CD4 + T cells and macrophages could directly result in allogeneic graft rejection [10,16,40,41]. Considering that allogeneic grafts have severe inflammatory infiltration, such as CD4 + T cells and macrophages, we postulated that IL-27Rα may act as a targeted biomarker to monitor acute allogeneic graft rejection, based on graft inflammatory cell infiltration, non-invasively and visually.…”

Inhibition of Pim2-prolonged skin allograft survival through the apoptosis regulation pathway

“…22 Furthermore, in our previous study, an approximately fivefold overexpression of the pim2 gene, as determined by sequencing-based serial analysis of gene expression, was detected in the allograft-activated CD4 1 T cells, which suggests a potential role of the Pim2 kinase in allograft rejection. 23 Considering all of the aforementioned results, we hypothesize that the Pim2 kinase may participate in allograft rejection through targeting the apoptosis of CD4…”