Grant: Project Grant

Autoimmune diseases result from a dysfunction of the immune system in which immune cells attack the body's own organs, tissues and cells. Guillain Barré Syndrome (GBS) is an autoimmune disease in which the immune system attacks the peripheral nerves. Two thirds of cases are preceded by virus or bacterial infection. Patients suffer from numbness, weakness and pain in the legs which spread to the arms and upper body. The symptoms can increase in intensity until the affected person is almost totally paralyzed. It is the most common acute paralysis and represents a serious emergency in neurology. GBS also causes severe persistent disability in a significant number of patients. Although pathological changes have been well established with massive immune cell infiltration into the nerves, which results in destruction of the myelin sheath (a structure that protects nerve cells) and the nerve fibers themselves, many fundamental questions remain to be answered: Why so many people have virus or bacterial infections, but only a small population develop GBS? Where is the site of the abnormality that initiates the disease process? What are the key molecules or cells that determine the fate of the disease? Why some patients recover spontaneously, while others not? We observed that B7.2 transgenic mice and WT mice infected with cytomegalovirus exhibit some abnormal symptoms, which mimic clinical and pathological features of GBS in humans. In the current proposal, we will use these two settings to dissect the molecular and cellular mechanisms leading to the initiation, progression and recovery of the disease. We will focus on the roles of two types of major immune cells, T lymphocytes and macrophages, to understand how these cells normally present in the blood can move into peripheral nerves and damage the nervous tissue. Our investigation will contribute to the development of more efficacious and clinical applicable therapeutic strategies for the mil