Harnessing Host for Graft-versus-Host
Therapeutic manipulation of immunosuppressive type 1 regulatory T cells may help to prevent graft-versus-host disease
People who receive bone marrow, organs or other tissues from donors stand at risk of a major complication that their immune systems will reject those grafts. But sometimes immune threats are a two-way street. Graft-versus-host disease is a common, life-threatening complication in which cells from a donated graft attack the host tissues of the person who receives the transplant.
One potential therapeutic strategy for graft-versus-host disease involves harnessing the immunosuppressive properties of type 1 regulatory T (TR1) cells, which play an important role in maintaining immune tolerance and limiting inflammation during autoimmune disease and after infections. However, the lack of knowledge about the development and functions of these cells has limited their therapeutic use.
In a study published April 7, 2017 in the journal Science Immunology, Ping Zhang and colleagues at QIMR Berghofer Medical Research Institute in Brisbane, Australia and the Royal Brisbane and Women’s Hospital delineated the molecular circuits driving TR1 cell development and examined their functions after bone marrow transplantation in mice.
Notably, TR1 cells were the most abundant regulatory T cell population after bone marrow transplantation in mice and were also abundant in blood samples from human bone marrow transplant recipients. Additional experiments showed that these cells produce a protein called Eomesodermin, which acts in concert with a protein called Blimp-1 to promote TR1 cell development. Moreover, Eomesodermin-producing TR1 cells were critical for the prevention of graft-versus-host disease in mice.
A better understanding of how TR1 cell development is regulated could pave the way for novel clinical strategies to prevent and treat graft-versus-host disease and other diseases characterized by excessive, harmful immune responses.