X-Message-Number: 17869
From: Brent Thomas <>
Subject: ischemia damage moderated by altered T-Cells
Date: Thu, 8 Nov 2001 13:10:47 -0500 

An interesting note from UniSci about some experiments with ischemia that
seem to indicate there
may be processes involving T-Cell function that increase damage. Perhaps
strategies to moderate
T-Cell activity during ischemic events could increase odds of survival with
minimal damage...

from: http://unisci.com/stories/20014/1108013.htm

During Ischemia, One Type Of T Cell Acts Strangely
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
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
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.
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;
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
Hospital at Harvard Medical School, Boston. - By 
Karen Blum
(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 websites:
The Johns Hopkins Comprehensive Transplant Center
The Journal of Clinical Investigation
[Contact: Karen Blum]

Brent Thomas

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