Skin transplants often face rejection by the immune system, but research shows skin grafts may be pre-treated with dendritic cells before the transplant to prevent organ rejection.
In 2016, more than 33,000 organ transplants occurred in the U.S. After a person receives a transplant, the immune system may attack the organ as foreign. This can occur rapidly, within the first year, in about 15% of people who receive kidney transplants, for example. However, skin transplants are rejected at a much higher rate for reasons that are not fully understood. Researchers of Brigham and Women's Hospital embarked on research studies to determine the cause of skin transplant rejection by the immune system and how this can be prevented.
The research involved using a MHC-mismatched murine skin allograft model. When signs of transplant rejection were observed, a number of studies were conducted, including among other assays, isolation and quantification of skin immune cells. The researchers observed the presence of a specific dendritic cell subtype, CD103+, that seems to play a significant role in organ rejection. Dendritic cells are powerful antigen-presenting cells that provide signaling for specific T-cell activation.
The dendritic cells of the donor tissue provoked the immune response directly by interacting with the host T cells or indirectly by transferring MHC to the host dendritic cells. The absence of donor CD103+ dendritic cells led to less T-cell priming and longer skin transplant survival. DnaK can reduce MHC on the CD103+ dendritic cells by incubating the skin grafts with the anti-inflammatory mycobacterial protein and therefore increasing skin transplant survival. Experiments with human dendritic cells in vitro showed that pre-treating them with Dnak impedes their ability to prime T cells.
The research findings suggest the possibility of a fresh approach to prevent alloimmunity by targeting MHC molecules, particularly MHC-II on CD103+ dendritic cells. This can entail the direct treatment of donor organs before transplantation. The strategy is quite distinct from the conventional approach of treating the patients with immunosuppressive drugs in an attempt to prevent tissue rejection. Although this may still be used, it can be complemented with the pre-treatment approach to fill in mechanistic gaps not addressed with immunosuppressive drugs.
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Reference:New Insights Into What Drives Organ Transplant Rejection. (2018). Electronic Component News. Retrieved 4 October 2018, from https://www.ecnmag.com/article/2018/09/new-insights-what-drives-organ-transplant-rejection