The immune system identifies and attacks threats to our bodies, such as invading bacteria or viruses, and has systems to recognize what tissues are part of our selves. When an organ is transplanted, the immune system treats it as an invader and attack – just like it would for a bacterial infection. This is the core mechanism behind rejection in transplantation.
Although organ transplantation is a highly effective therapy for organ failure, rejection remains a major concern. To reduce the likelihood of rejection, post-transplant patients must take immunosuppressant drugs for the rest of their lives. While immunosuppressants have made modern organ transplantation possible, they weaken the immune system, making the patient susceptible to serious health risks ranging from infections and diabetes to kidney dysfunction and cancer. Therefore, immunosuppressant drugs limit the long-term effectiveness of organ transplantation.
Immune tolerance is a state in which the immune system does not reject the donor organ while still responding to challenges from the environment, such as infections. Tolerant post-transplant patients do not require immunosuppressive drugs and their new organs function normally. Achieving tolerance is possible in animals but has only been documented in limited circumstances in humans.
Drug-free transplant acceptance (tolerance) would greatly enhance the benefits of transplantation. Our ultimate goal is to develop approaches to establishing robust tolerance in patients, so that we could treat end-stage organ diseases of the lung, kidneys, liver, and heart with a single organ transplant procedure, and restore function and quality of life without the need for immunosuppressive drugs. We aim to develop diagnostics that will help us identify and monitor tolerance in the clinical setting and protocols to induce tolerance in transplant recipients.