Research shows how tissue-derived T cells can damage other organs in stem cell transplant patients



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Every year, more than 40,000 allogeneic hematopoietic stem cell transplants are performed worldwide. Very often there is a so-called graft reaction against the host-inflammatory disease, which can affect various organs and is caused by an unwanted protective reaction of donor cells and the body’s own T cells.

Scientists at CeMM, Vienna Medical University and LBI-RUD, led by Georg Stary, are now showing how these endogenous T cells, derived from tissues, penetrate through the blood into other organs, such as the gut, and contribute to inflammation. The study provides important approaches to improving stem cell transplant therapy and new diagnostic possibilities. It was published in the Journal of Experimental Medicine.

Stem cell transplantation is an important, necessary method of treatment, especially for patients with leukemia. According to the annual transplant report for 2020, in Austria alone in 2019, 630 such transplants were performed. In this process, all the blood cells of the affected patient first die with chemotherapy and radiation and are then replaced by healthy bone marrow or blood stem cells. from the donor. Approximately half of patients develop inflammatory skin diseases after transplantation with serious consequences. T-cell rejection is one of the leading causes of death after hematopoietic stem cell transplantation.

In a previous study, a team of researchers led by dermatologist Georg Stary of the CeMM Molecular Medicine Research Center of the Austrian Academy of Sciences, Vienna Medical University and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases was able to determine the mechanism causing this graft-versus-host disease. ). In skin samples taken from patients before and after transplantation, the old and study author Johanna Strobl (MedUni) were able to show that T cells derived from the host in skin tissues are responsible for inflammatory responses.

T cells of the skin that live in the tissues migrate into the blood

In their current study, using a new model, Strobl and co-author Laura Marie Gale (CeMM / LBI-RUD) show that these skin T cells that live in tissues can be found in the blood of stem cell transplant patients. “The migration of inflammatory skin T cells derived from tissues into the blood creates a risk of transmitting skin inflammation to other organs. Especially in the gut, which is often affected by HPV, we found a surprising number of cells that are originally from the skin,” the study authors say.

T-cell inactivation as a possible approach to improving therapy

For their study, Strobl, Gale, and Starry investigated circulating T cells in the blood using samples from stem cell transplant patients. Using a special tracking method, the researchers were able to distinguish exactly which T cells from the donor and which from the patient.

Once all the blood cells had already been killed by chemotherapy, we were able to conclude that the detected T cells could only come from the tissue. With the help of various markers they can be traced to the skin.

George the Elder, head of the research group

Blood sample instead of biopsy

The study also provides indications for an additional important diagnostic aspect. The authors of the study were able to notice that in the blood, depending on the clinical picture, more circulating T cells are found in patients with stem cell transplantation. Accordingly, it is quite possible to imagine that in the case of skin or tissue diseases it is possible to perform a blood test and assess the phenotype of T cells derived from the skin, instead of a long and often unpleasant sample of the affected. area. “This procedure will be a kind of‘ liquid biopsy ’in the case of inflammatory reactions in the tissues,” the study authors say.

Source:

CeMM Molecular Medicine Research Center of the Austrian Academy of Sciences

Magazine link:

Strobl, J., et al. (2021) T-cells of a human resident come out of the skin and mediate systemic inflammation caused by Th2. Journal of Experimental Medicine. doi.org/10.1084/jem.20210417.

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