- Dr. Qizhi Tang, Principal Investigator
- Mr. Mingying Bi, Research Associate
- UCSF Diabetes Center, San Francisco, USA
- Visualizing Regulatory T Cell Control of Islet Transplant Rejection
One of the fundamental properties of the immune system is the ability to distinguish healthy self-tissue from infected, cancerous or foreign tissues. Thus, when tissue from one individual is transplanted onto another, the immune system mounts a vigorous response to eliminate the transplant, a process referred to as alloimmunity. The situation is further complicated in patients with type-I diabetes, whose immune system fails to refrain from attacking normal tissues, destroying the insulin-producing β cells in the pancreatic islets leading to the loss of blood glucose control. Such immune-mediated self destruction is referred to as autoimmunity. One promising approach to restore β cell function in these individuals is islet transplantation. However, the newly transplanted islets become targets for both alloimmune and autoimmune rejection. Generalized immunosuppression can prolong the graft survival, but such treatments are associated with high toxicity and make patients more susceptible to infections and cancer. Thus, we need to develop a novel therapy to specifically fend off the alloimmune and autoimmune attacks while preserving other immune functions. A small population of white blood cells called regulatory T cells (Tregs) has been critical for preventing autoimmunity. However, the normal level of Tregs is not sufficient to protect against potent alloimmune responses. We propose that increasing Treg numbers will control both the allo- and autoimmune responses in diabetic islet graft recipients. The goal of the research proposed in this grant application is to develop such treatments in mouse models, and to investigate the mechanisms of Treg control of allo- and autoimmunity. We will monitor both types of the immune responses from its initiation in the lymph nodes to graft rejection in vivo and determine which processes are controlled by Tregs. Results from these studies will help us to design better treatments by harnessing the body’s powerful self-control mechanism.