- Dr Benjamin Medoff, Principal Investigator
- Dr Josalyn Cho, Research Associate
- Dr Marly Roche, Research Assistant
- Massachusetts General Hospital, Boston, USA
- The Role of the Immune Protein TIM3 in Lung Transplantation
For patients with end-stage lung disease, lung transplantation can improve quality of life and lead to longer survival. However, only 50% of patients are alive 5 years after their transplant. The major obstacle in lung transplantation is airway scarring, so-called bronchiolitis obliterans (BO), which results from repeated injuries to the airways. Rejection, an immune-mediated reaction against the transplanted organ, is the major source of this injury. Because of this, transplant patients take powerful medications that suppress the immune system and have dangerous side effects. If the transplant recipient’s immune system could be suppressed in a more specific fashion then the patient could avoid the use of these medications. Transplants are rejected by immune cells called effector T cells. These T cells express damaging proteins and can directly injure the lung. TIM3 is a protein expressed on activated effector T cells that seems to decrease their harmful activity. In other diseases, such as multiple sclerosis, it was found that effector T cells have low levels of TIM3, suggesting that there was less control of the T cells, leading to more disease. We hypothesize that TIM3 expression on effector T cells will inversely correlate with the incidence of rejection and BO following lung transplantation. Furthermore, we suspect that TIM3 can modulate T cells in the lungs of these patients. In our grant, we will study the relationship between TIM3 expression on T cells isolated from patients who have had lung transplants and the incidence of rejection and BO. We will then see if manipulation of TIM3-activity can modulate the effector functions of these T cells. We will also investigate the mechanisms by which TIM3 controls these T cells. Our proposal may lead to a novel means of reducing the incidence of rejection and BO in transplanted lungs.