Mechanism of unwanted rejection identified in stem cell transplantation

In the treatment of leukemia, stem cell transplantation following chemotherapy and radiotherapy can often cause severe adverse inflammatory reactions, especially in the skin or intestines, as these so-called barrier organs are more frequently affected. Until now, the reason for this was unclear. A MedUni Vienna team led by Georg Stary and Johanna Strobl of the MedUni Vienna Department of Dermatology, the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases has now identified an immune mechanism partially responsible for this. The results have now been published in the leading journal Scientific translational medicine.

The term leukemia is used to describe a group of malignant diseases of the hematopoietic system, in which the precursors of white blood cells (leukocytes) proliferate uncontrollably. Chemotherapy and radiation therapy are used to destroy abnormal blood cells, which are then replaced by a stem cell transplant. In leukemia, transplantation of healthy bone marrow stem cells or hematopoietic stem cells is often the only hope of recovery for patients. The process involves “replacing” all of the recipient’s blood cells that were previously destroyed by treatment with donor cells.

However, MedUni Vienna dermatologists have now discovered that there are so-called T cells resident in the skin and inactive in the endogenous immune system that survive chemotherapy and radiotherapy intact and continue to survive for another ten years between and under the la epithelial cells. skin, while circulating T cells are destroyed.

“We were able to show that surviving T cells in skin tissue are responsible for the inflammatory reaction following a stem cell transplant. These phenomena often occur within the first 100 days and can cause anything from mild eczema. to extensive fibrosis, hardening of the tissue, or blistering of the skin surface. In other words, endogenous T cells attack the recipient (host) after stem cell transplantation. ” In specialist parlance, the condition is also called Graft versus Host Disease (GvHD) and, for the first time, this study identified a reverse “host versus graft reaction”.

There have also been instances where donor T cells have further “supported” and thus intensified this reaction. Affected patients are treated with cortisone, which causes an additional burden for patients who are already immunosuppressed following the transplant. The study found that in patients who do not develop graft-versus-host disease, T cells residing in the remaining tissues after treatment even proved beneficial to the recipient as they took on their role in immune defense and protection from infections.

In the future, the study’s exemplary results could lead to novel treatment strategies that help avoid, or at least minimize, unwanted and violent inflammatory reactions following stem cell transplants by manipulating the recipient’s inactive T cells in advance. Furthermore, manipulation of tissue-resident T cells could lead to new therapeutic approaches for other chronic inflammatory skin diseases, such as psoriasis or neurodermatitis.