Immunological profiling in kidney transplantation through high-dimensional analysis

Abstract

This thesis investigates the immunological effects of mesenchymal stromal cell (MSC) therapy in the context of kidney transplantation, with the intent to improve long-term graft survival and reduce the need for nephrotoxic immunosuppressive drugs. Technical innovations were first established by optimising mass cytometry protocols, including live-cell barcoding and the use of frozen antibody mixes to ensure reproducibility and high-quality single-cell analysis.

Subsequent studies explored immune dynamics following both autologous and allogenic MSC infusion in kidney transplant recipients. Using high-dimensional single-cell analyses, MSC therapy was shown to induce significant alterations in peripheral immune cell subsets. Remarkably, rapid immune changes in B and T cell phenotypes were observed as early as four hours post MSC infusion.

The thesis also examined the role of indoleamine 2,3-dioxygenase (IDO) expression in glomerular endothelial cells of transplanted kidneys with glomerulitis, revealing its association with local immune activation.