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View Article and Find Full Text PDFThe three-dimensional organization of the genome in mammalian interphase nuclei is intrinsically linked to the regulation of gene expression. Whole chromosome territories and their encoded gene loci occupy preferential positions within the nucleus that changes according to the expression profile of a given cell lineage or stage. To further illuminate the relationship between chromosome organization, epigenetic environment, and gene expression, here we examine the functional organization of chromosome X and corresponding X-linked genes in a variety of healthy human and disease state X diploid (XX) cells.
View Article and Find Full Text PDFCD8 induced regulatory T cells (iTregs) have been identified to suppress alloreactive immune responses and expressed regulatory T cell (Treg) ontological markers as similar as CD4 iTregs. However, adoptive transfer of CD8 iTreg-based therapy is hampered by the instability of Treg specific-transcription factor, Foxp3. As CD8 iTregs were previously demonstrated to possess superior tumor-killing ability to CD4 iTregs, adoptive transfer of stabilized CD8 iTregs would be a potential therapy to prevent tumor relapse during graft-versus-leukemia disease (GVHD) treatment.
View Article and Find Full Text PDFThere is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality.
View Article and Find Full Text PDFDonor-specific CD4CD127CD25FOXP3 regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination.
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