- Dr. Fadi G. Lakkis, Principal Investigator
- Dr. Nancy Ruddle, Research Associate
- Dr. Fady K. Baddoura, Research Associate
- Yale University School of Medicine, New Haven, USA
- Long-Term Acceptance of Transplanted Organs
Indefinite acceptance of a transplanted organ without continuous intake of immunosuppressive medicines is a desirable but elusive goal for patients with end-stage kidney, liver, heart, or lung disease. Attempts to achieve this goal have traditionally focused on methods to alter the patient’s immune response so that it does not respond to and reject the foreign organ, a phenomenon referred to as immunologic tolerance. Safe and effective induction of transplantation tolerance, however, has proven to be very difficult in humans. Here, we suggest an alternative and possibly complementary approach to achieving long-term acceptance of transplanted organs by a mechanism known as immunologic ignorance. Immunologic ignorance occurs if communications between the transplanted organ and the patient’s immune system are interrupted so that the immune reaction that leads to rejection is not initiated.
In order to begin to understand how to achieve immunologic ignorance, we propose to first determine why foreign organs almost always initiate immune responses even after they have had a chance to recover from the trauma of the transplantation procedure. Specifically, we wish to explore whether specialized cell aggregates, known as tertiary lymphoid tissues, form within the transplanted organ and allow for direct communication between the cells of the organs and those of the patient’s immune system leading to either rapid (acute) or slow (chronic) rejection. This type of analysis would allow us to identify therapeutic strategies to block tertiary lymphoid tissue formation and help patients extend the survival of their transplanted organs.