Research Group
- Dr. Hamid Rabb, Principal Investigator
Location
- Minneapolis Medical Research Foundation, Minneapolis, USA
Title
- Mechanisms of T-Cell-Mediated Injury after Renal Ischemia Reperfusion
Kidney ischemia is the main cause of the initial poor function of an organ transplant. Kidney ischemia predisposes to acute rejection, which in turn predisposes to chronic rejection - the major long-term cause of graft loss. There is no specific treatment for kidney ischemia. Recently, we and others have identified that the circulating T cell is an important mediator of kidney ischemic damage. This was somewhat of a surprise finding, as the T cell is known to be important in rejection, but not in organ procurement injury.
The observation that the T cell is a mediator of kidney ischemia has been well verified in experimental models. However, the underlying mechanisms for this are unknown. We therefore propose to begin to elucidate these underlying mechanisms. Based on our preliminary data using a mouse model of kidney ischemia, we hypothesize that a major subset of T cells, called Th1, functionally mediates T cell-mediated kidney injury, and that T-cell-mediated injury requires engagement of a key receptor on the surface of the kidney.
We plan to test this hypothesis using an established mouse model of kidney ischemia, various strains of generated mutant mice, sensitive measures of kidney function, and molecular and cellular detection techniques. Our results will have implications for the understanding of organ procurement injury and may help lead to new therapies. In addition, the results will also extend and challenge our basic understanding of the immune system.
