In an example of biological irony, the same white
blood cell chemistry known to damage kidneys used for
transplants may also help prevent such damage, according to
a federally funded study in genetically engineered mice at
Researchers have long known that when blood flow is
cut off and then returned to transplanted kidneys or other
organs, immune system cells called T lymphocytes produce
toxic natural chemicals that contribute to ischemic
reperfusion injury. Nature cannot distinguish between
deliberate surgical wounds needed to remove and re-implant
a donor kidney and other kinds of organ damage in which
certain toxic chemicals are needed to clean up or remove
But in a study published in the September issue of
The Journal of Immunology, the Hopkins team reports
that T cells can also play a role in reducing cellular
damage in IRI kidneys, according to Hamid Rabb, medical
director of kidney and pancreas transplantation at the
School of Medicine.
Ischemic reperfusion injury, or IRI, occurs in 30
percent to 40 percent of kidneys removed from dead donors,
resulting in lower kidney survival rates, shortened kidney
life and a cost increase of approximately $20,000 per
patient from the initial hospital stay and treatment alone,
Rabb said. Scientists therefore are interested in
identifying means of preventing or rapidly treating IRI,
but one barrier to greater understanding has been the
inability to detect the lymphocytes in the kidney during
the first critical six hours after blood flow is
In the Johns Hopkins study, designed to try to find
these cells and learn more about IRI, white blood cells
were taken from mice that had undergone experimentally
induced IRI. These cells were injected into mice engineered
without a thymus gland, which produces T cells. A
comparison group of genetically engineered mice got no
After the researchers temporarily stopped blood flow
to kidneys in mice in both groups for 30 minutes, they
discovered that the kidneys in the injected mice were
improved compared to the other group of mice.
This was an unexpected result, Rabb said. "For years
we have known that T cells play a role in IRI, but we
assumed it was always a negative role; now we know they
play a protective role as well."
Rabb said that further research is needed to establish
the exact mechanism for this protection but, he said, it
makes perfect sense in theory.
"T cells are part of our immune system, and our immune
system is designed to protect us from injury. What's
surprising here is that practical experience over the years
has taught us that when the immune system is activated, we
have increased cell damage," he said.
Using a new method developed by Dolores B. Ascon, a
postdoctoral fellow in the Department of Nephrology and
first author on the paper, Rabb and his team successfully
tracked small numbers of lymphocytes in three distinct
groups of mice: normal mice, mice that underwent fake
surgery without blood flow interruption to the kidneys
(ischemia) and mice that underwent surgery and 30 minutes
The study showed elevated levels of T cells in the
kidneys three hours after IRI compared to the normal mice.
It also showed elevated levels of the chemicals tumor
necrosis factor alpha (TNF alpha) and interferon gamma (IFN
gamma), which are known to produce cellular damage in
kidneys. These chemicals are produced by T cells.
The mice that underwent fake surgery also had an
elevated level of T cells when compared to the normal mice,
but these cells did not release TNF alpha and IFN gamma and
did not cause injury to the kidneys.
In this case it appears as though the surgery
triggered the movement of T cells to the region, but since
there was no ischemia, these cells did not produce TNF
alpha and IFN gamma, Rabb said. This only further
illustrates the complexity of the role T cells play in
Other contributors to this study are Sergio Lopez
Briones, Manchang Liu, Miguel Ascon, Vladimir Savransky and
Mark J. Soloski, all of the Department of Medicine at the
Johns Hopkins School of Medicine, and Robert B. Colvin, of
the Department of Pathology at Harvard Medical School.
This study was supported by grants from the National
Institutes of Health.