JCI: Exocystopic tissue host T cells survive hematopoietic stem cell transplantation and promote graft resistance to host disease.

August 31, 2020 /--- -- An allogeneic hematopoietic stem cell transplant (HSCT) is the injection of healthy hematopoietic stem cells from the recipient as part of a potential treatment for cancer.
although the treatment can save lives, its main complication is graft anti-host disease (GVHD), which can lead to significant morbidity and can be fatal.
patient receives a conditioning regimen, a chemotherapy designed to remove normal white blood cells, including T-cells, before an allogeneic hematopoietic stem cell transplant.
in a new study, researchers from Bligen Women's Hospital in the United States, the University of Oslo in Norway and the University of Newcastle in the United Kingdom found that the subject's skin and intestinal T-cells were able to survive conditioning programmes and continue to function normally.
, however, under certain conditions, these T-cells can be activated by the provider's white blood cells and play a previously neglected role in acute GVHD.
study was recently published in the journal Journal of Clinical Investigation under the title "Perseon host T cells survive hematopotic stem cellation and promote graft-versus-host disease".
photo from Journal of Clinical Investigation, 2020, doi:10.1172/JCI129965.
Thomas Kupper, head of dermatology at Bregan Women's Hospital, said: "Over the years of research into GVHD, it has been a belief that transplant T cells mediate the disease and attack the body.
in the skin and gastrointestinal tract, the T cells that cause GVHD also come from the host -- the patient's own T cells.
these persistent T-cells from the host are activated by the graft cells, causing tissue damage.
this completely novel discovery unexpectedly opened the door to the development of new ways to treat and prevent the disease.
" conditioning program is designed to remove normal white blood cells, including T-cells, from the host body to make room for the transplant to form a new immune system.
T-cells are difficult to detect when the subject's blood is examined after conditioning.
kupper and colleagues found that although the T cells in the subject's blood had been removed, the tissue T cells in the subject's skin and intestines were still present.
The researchers analyzed T-cells for high-volume DNA sequencing and short tandem repeat sequences (short tandem repeat, STR) to jointly determine the proportion of blood (or tissue) cells from the recipient (transplant) or recipient (host), respectively.
they further studied male-female host/provider mismatch transplants and used XY chromosomes to determine the source of these cells.
they also used mouse models to transplant human skin into mice with low immunity to avoid rejection and to test the host skin T-cells' ability to mediate GVHD without the provider's T-cells.
based on high-volume sequencing and STR analysis, Kupper's team observed that during GVHD, there were still large numbers of host T cells present in the skin and small intestine, even though 100% of the blood cells were the source of the provider.
in mouse models, they found that skin-resident host T cells could be activated by donor non-T cell white blood cells, leading to GVHD-like skin inflammation.
these results suggest that, surprisingly, skin and intestinal resident T cells not only survive in conditioning programmes, but also exist in tissues during acute GVHD and are likely to play an important role in the pathophysiology of the disease.
Our new understanding of GVHD allows us to see tissue residering memory T cells in the host/subject as a new therapeutic target, which could be a game-changer," Kupper said.
assume that we can use this information for early intervention and even to prevent the advent of GVHD.
study is an example of how we can never assume that we know everything about the mechanisms of disease and must always be willing to challenge mainstream views.
" (bioon.com) Reference: 1. Sherrie J. Divito et al. Perity host T cells survive hematopoietic stem cellation and promote graft-versus-host disease. Journal of Clinical Investigation, 2020, doi:10.1172/JCI129965.2.Host tissue T cells may have an unexpected role in graft-versus-host disease.