Hematopoietic Stem Cell Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) is used as a treatment for many hematological malignancies and disorders. Patients are first given various treatments to destroy malignancy and to suppress own blood production (hematopoiesis), and then healthy donor-derived stem cells are given to restore the hematopoiesis.

Graft-vs-Host Reaction

Apart for stem cells, graft contains a mixture of various types of mature immune cells essential for stem cells to engraft, to keep patients free of infections (until their immune system is restored) and fight off remaining pathogenic cells, e.g. create the so called Graft-vs-Leukemia effect. However favorable reaction of immune cells in the graft is counterweighted by the harmful Graft-vs-Host Reaction, where graft immune cells attack patient tissues and cause inflammation, most commonly skin, gut and liver. In severe cases this inflammation can be lethal. The major driving force behind both favorable and harmful effects is T-cells. Research of the past decade has been focused on suppressing the Graft-vs-Host reaction specifically while sparing beneficial effects.

T-cells

There are different types of T-cells. The small fraction of T-cells termed as T-regulatory cells have the ability to specifically control the Graft-vs-Host reaction, without affecting favorable effects of immune reactivity. These cells are a central part of the tolerance network. The diversity of T-regulatory cells itself necessitates their detailed characterization and analysis in stem cell donor grafts and transplant patients.

Our goal

A goal of the research in our group is to understand the biological tolerance networks in allogeneic hematopoietic stem cell transplantation, in particular the contribution of donor and patient regulatory T cell subpopulations to tolerance.
Our findings indicate that Treg subpopulations differ significantly in their ability to protect from Graft-vs-Host reaction. Further studies are underway to understand the characteristics by which they differ. We study T reg subpopulations ability to expand, which are the necessary conditions, and which of the receptors enable Tregs to traffic to certain tissues (i.e. skin, gut). These and other findings enable a graft composition that might enhance specific T regulatory subpopulations and improve outcome of allogeneic hematopoietic stem cell transplantation.