Nov. 7, 2001 Ischemia, or an interruption in blood flow to tissue, greatly decreases the success of transplanted kidneys. There's no specific treatment, partly because physicians don't know exactly how the injury occurs. But now, a new study shows that in mice, at least, tiny molecules within specialized immune system cells may hold some clues.
Reporting in the current issue of The Journal of Clinical Investigation, a team led by Hamid Rabb, M.D., medical director of the kidney transplant program at Johns Hopkins, shows that during ischemia, one kind of these so-called T cells acts out of character.
The cells in question are CD4 cells, best known as the cells targeted by HIV. Also called helper T cells, they help identify, attack and destroy specific bacteria, fungi and other germs that infect the body by regulating the production of antibodies (proteins that fight infections) and cytokines (chemicals that regulate other immune functions).
During the study, researchers compared mice specially bred without CD4 cells to normal mice with induced ischemia and kidney failure, and found that the mice without CD4 cells were about 40 percent better protected from damage. When normal CD4 cells were reintroduced into the genetically altered mice, the amount of ischemic damage increased, further demonstrating that during ischemia, the CD4 cells somehow helped mediate the damage. Two CD4 cell molecules – CD28 and IFN-gamma – were identified as participating in the injury process.
"This challenges our ideas of what T cells do, and provides a novel avenue for developing therapies to minimize or reverse ischemic damage," Rabb says. "The exciting thing is we think this finding can apply to all areas of ischemia, including that caused by strokes and heart attacks."
Additional research will investigate the mechanism by which CD4 cells operate in ischemia, Rabb says.
The study was supported in part by the National Institutes of Health and the National Kidney Foundation. Other authors were Melissa J. Burne of Hopkins; Frank Daniels, Asmaa El Ghandour and Michael P. O'Donnell of Hennepin County Medical Center at the University of Minnesota, Minneapolis; and Shamila Mauiyyedi and Robert B. Colvin of Massachusetts General Hospital at Harvard Medical School, Boston.
Reference: Burne, M.J., et. al., "Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure," The Journal of Clinical Investigation, Nov. 2001, Vol. 108, No. 9.
Related Web sites:
The Johns Hopkins Comprehensive Transplant Center http://www.hopkinsmedicine.org/transplant
The Journal of Clinical Investigation http://www.jci.org
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