Host versus Graft

Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure in which healthy hematopoietic stem cells from a donor are injected into a recipient as part of the therapy of blood tumors. This strategy can save a patient's life, but a serious complication is the development of graft-versus-host disease, which significantly complicates the condition and can lead to death. Before allogeneic HSCT, the patient undergoes conditioning – chemotherapy designed to deplete his own white blood cells, including T cells. But a new study conducted by researchers from Brigham Women's Hospital (USA), the University of Oslo (Norway) and Newcastle University (UK) has shown that T-cells of the recipient's skin and intestines survive after conditioning and continue to perform their normal functions. Under certain conditions, these T cells can be activated by donor leukocytes and play a previously underestimated role in the acute graft-versus-host reaction.

Previously, it was believed that transplanted donor T-lymphocytes mediate the disease and attack the patient's body. Now, researchers have shown that the T cells that trigger the graft-versus-host reaction originate from the host, that is, from the patient's own T cells. These resistant recipient T cells are activated by cells from the transplant, which leads to tissue damage. This new unexpected discovery opens the door to new approaches to the treatment and prevention of graft-versus-host disease.

The conditioning regime is designed to destroy the patient's white blood cells, including T cells, to make room for a new immune system that will develop from the transplant. When the recipient's blood is examined after conditioning, T cells are usually not detected. But Thomas Kupper and his colleagues have shown that even if T-cells are absent in the recipients' blood, their tissue T-cells in the skin and intestines are preserved. The researchers used high-throughput DNA sequencing of T cells and analysis of short tandem repeats (STR analysis), which together determine the proportion of blood cells (or other tissue) originating from a donor (transplant) or recipient (host). They further studied the reaction between male and female donors/recipients, using XY sex chromosomes to determine the origin of cells. The team also used mouse models, transplanted a fragment of human skin into mice with weakened immunity (to avoid rejection) and tested the ability of host skin T cells to mediate a graft-versus-host reaction without donor T cells.

After receiving the results of high-throughput sequencing and STR analysis, the group saw that many host T cells were still present in the skin and small intestine during the graft-versus-host disease, even when the blood cells were 100% of donor origin. Mouse models have demonstrated that host T cells in the skin can be activated not only by donor T cells, but also by other white blood cells to cause skin inflammation similar to a rejection reaction. The results show that T-cells of the skin and intestines not only survive after conditioning, but are also present in tissues during an acute graft-versus-host reaction and very likely play an important role in the pathophysiology of this disease.

A new understanding of the graft-versus-host disease makes it possible to think of recipient memory T cells as a promising target for therapy before allogeneic HSCT. Hypothetically, if we intervene in advance, it will be possible to prevent the development of a graft-versus-host reaction.

Article by S.J.Divito et al. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease is published in the Journal of Clinical Investigation.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to EurekAlert: Host tissue T cells may have an unexpected role in graft-versus-host disease.