by Mark Wheeler
In a first step toward a possible strategy to offset the ravages of type 1 diabetes and other autoimmune diseases, scientists at City of Hope have discovered how an obscure but critical component of the immune system functions.
Reporting in a recent issue of the Journal of Immunology, Chih-Pin Liu, Ph.D., associate professor in the Division of Immunology, Cyndi Chen, Ph.D., a City of Hope graduate student, and colleagues report the underlying mechanisms for a critical part of the immune system called a regulatory T-cell (Tr-cell). Understanding how Tr-cells work should help in the design of a new strategy that can effectively prevent or even reverse various autoimmune diseases in humans.
Most autoimmune diseases are caused by a malfunctioning immune system, when T-cells mistakenly identify their own host as a foreign object and attack it. But while some types of T-cells that have turned pathogenic or cause disease play a role in the onset of autoimmune diseases, other types help prevent such diseases.
Such is the case with regulatory T-cells. As their name implies, various types of Tr-cells regulate the immune system by inducing immune tolerance, a process in which the immune system disregards molecules native to the host but attacks and destroys foreign molecules. Depending on the type of Tr-cells, which are activated by recognizing antigens (proteins that trigger an immune response), a deficiency in the number or function of Tr-cells can lead to a breakdown in immune tolerance and to the development of autoimmune diseases like type 1 diabetes or multiple sclerosis (MS).
“An important strategy we are pursuing to treat or prevent autoimmune diseases is to restore the function and number of these Tr-cells,” said Liu, “and a critical step was to understand how they function.”
In this current work, the researchers did just that, discerning that a particular line of Tr-cells in mice operate through a complicated cascade of events: the secretion of various messenger cytokines (protein molecules that communicate between immune system cells); physical contact with the pathogenic T-cells; and the stimulation of antigen-presenting cells that release signaling molecules, like nitric oxide, which suppress the growth of pathogenic T-cells and inhabit the disease.
Most promising of all, said Liu, is that activated Tr-cells also suppress other, unrelated pathogenic T-cells that are specific for an entirely different antigen. This suggests these Tr-cells can also regulate different pathogenic T-cells that cause other autoimmune diseases. “This is what makes this research so potentially exciting,” said Liu. “We may have found a way to generate an unlimited number of Tr-cells that can be used in the treatment of various autoimmune diseases.”
Ultimately, Liu said, these findings may lead to a new immunotherapy based on enhancing the function and increasing the number of Tr-cells that will induce or restore immune tolerance. His next steps are to determine whether these Tr-cells can protect people with diabetes who undergo islet cell transplantation, a process in which patients are given back the insulin-producing islet cells that have been destroyed by their own immune system. He also wants to determine what role these cells play in suppressing other autoimmune disease like MS. Finally, he and his colleagues plan to isolate similar populations of human Tr-cells to evaluate their effect on treating human autoimmune diseases like diabetes. Currently, type 1 comprises 5 to 10 percent of all diabetes cases, with roughly 30,000 new cases diagnosed each year.
