In the United States each year, half of the 2,000 patients on average who receive heart transplants eventually suffer from acute or chronic rejection of the donated organs. Researchers at The University of Toledo are working to decrease this and related organ rejection statistics, and are receiving financial support from the American Heart Association to do so.
Dr. Wenhao Chen, clinical assistant professor of medical microbiology and immunology, and Dr. Stanislaw Stepkowski, professor of medical microbiology and immunology, are principal and co-investigators, respectively, of a research program that received a $308,000 grant from the American Heart Association.
Titled “Identification of the Intracellular Regulators Involved Establishing T-Cell Tolerance to Cardiac Allografts,” the project investigates the molecular mechanisms that control how T-cells respond to transplants and other foreign bodies introduced to the body. The ultimate goal is to determine how these mechanisms can be manipulated to get T-cells to tolerate heart and other organ transplants.
T-cells — or T lymphocytes — are a major defense component of the human immune system that protects us from pathogen infections. However, upon transplantation, they also play a central role in rejecting transplanted organs.
“Heart transplantation is the only available therapeutic option for end-stage cardiac failures,” Chen said. “Since this is a life-supporting organ and the supply of transplantable hearts is extremely limited, it is critical to avoid heart graft loss due to immune rejection.”
He added, “Currently, heart-transplanted patients must take many immunosuppressive drugs daily. These drugs are associated with significant toxicities and increased risks for opportunistic infections and malignancy.”
Chen hopes that the body receiving the transplant can be prepared for it more successfully and without an extensive use of immunosuppressant drugs through a “selective and permanent inactivation/deletion of alloreactive T-cells” — the T-cells that can create problems for transplanted organs.
“In other words, we aim to terminate the T-cell responses to transplanted organs, while T-cell responses to pathogens should not be impaired,” Chen said.
Studying the intracellular regulators — the molecular mechanisms or proteins that negatively regulate the T-cells by selectively terminating their functioning — could lead to the eventual ability to control T-cell tolerance in this way.
“Immunologists have put great efforts to induce T-cell tolerance to transplanted organs during the last 50 years. I have been a researcher in this field during the last 12 years. We cannot achieve our research goal because we do not know the molecular mechanisms of T-cell tolerance,” Chen said. “Hopefully, our research will change this.”