Patients who receive stem cell transplants can develop severe adverse inflammatory reactions, mainly in the skin or gut, known as ‘graft-versus-host’ disease (GvHD). However, scientists in Austria have identified for the first time that host T cells resident in the skin could be partly responsible for this inflammatory disease, in what they call a ‘host-versus-graft’ reaction.
Dermatology researchers from the Medical University of Vienna studied skin and blood samples from patients undergoing stem cell transplant for a variety of blood cancers. They found that skin-resident T cells present before a transplant can survive conditioning chemotherapy and radiotherapy intact, while the circulating T cells are destroyed. They also showed that these skin-resident T cells can survive for at least ten years post-transplant.
Studying the role of these skin-resident host T cells in GvHD, they found that they can play a crucial role in the skin lesions, supporting and even intensifying the reaction – challenging the assumption that donor T cells are solely responsible. The work was published in the journal Science Translational Medicine.
The team was led by Georg Stary and Johanna Strobl from MedUni Vienna's Department of Dermatology, the CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. They said: “We were able to demonstrate that T cells surviving in the 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 through to extensive fibrosis, hardening of the tissue, or blistering on the surface of the skin. In other words, the endogenous T cells attack the recipient (host) following stem cell transplantation.”
Patients who did not develop GvHD benefited from tissue-resident T cells remaining after treatment because these cells assumed their role in immune defence and protecting against infection.
The authors say they hope their results could lead to new treatment strategies involving manipulating a patient’s inactive T cells in advance to minimise or avoid inflammatory reactions. The manipulation of tissue-resident T cells could also result in new therapeutic approaches for other chronic inflammatory skin diseases, such as psoriasis or neurodermatitis, they add.
Strobl J, Pandey RV, Krausgruber T, Bayer N, Kleissl L, Reininger B, Vieyra-Garcia P, Wolf P, Jentus MM, Mitterbauer M, Wohlfarth P, Rabitsch W, Stingl G, Bock C, Stary G. (2020) “Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease.” Science Translational Medicine, doi: 10.1126/scitranslmed.abb7028
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