Researchers will determine whether a specific molecule governs immune T cells’ “intolerance” to the body’s own tissues (as occurs in autoimmune diseases) and, conversely, “tolerance” to brain tumors that invade and take over brain cells.
Ironically, activation of immune T cells in autoimmune diseases results in destruction of the body’s own tissues, while therapies aimed at promoting attacks by T cells against aggressive brain tumors fail. T cells fail to attack brain tumors, in part because the tumors create an environment that suppresses initiation of these immune responses. Ordinarily, T cell responses are initiated through the cells’ interactions with “antigen-presenting cells” (APCs). These include immune macrophages and microglial and dendritic cells. APCs ordinarily capture, process, and present a specific invader to immune T cells. When this process goes awry in autoimmune diseases, somehow the body’s own tissues are misidentified as invaders. Conversely, the process fails to initiate an immune attack against brain tumors. The investigators, therefore, are studying how APCs either activate or turn-off immune T cells.
Whether or not APCs effectively initiate immune T cell attacks may depend on a molecule called “LR8.” The researchers hypothesize that this molecule is absent when T cells attack the body’s own tissues in autoimmune diseases, but present when T cells appropriately attack invaders. By studying T cell-APC interactions in tissue cultures in the lab and in a mouse model of autoimmune MS, the investigators will see whether manipulating the levels of LR8 alters the abilities of APCs to capture, process, and present a defined agent to immune T cells. The answer should help determine whether LR8 causes T cells’ destructive or protective actions, or is simply associated with those actions.
Significance: If this molecule is found to directly regulate T cells-APC interactions, the research may eventually lead to development of therapies that prevent T cell attacks in autoimmune diseases and transplantation and therapies that strengthen T cell attacks on brain tumors.