THE body’s need to conserve energy may be to blame for the proliferation of
diseases in which the immune system runs riot, says Barbara Fazekas of the
Centenary Institute of Cancer Medicine and Cell Biology in Sydney.
Fazekas’s theory could help explain the “hygiene hypothesis”—the idea
that the cleanliness of modern life leads to more allergies and autoimmune
diseases. If she is right, then trying to find “disease genes” may not be the
best way to tackle these disorders. “In a different environment, people with
those genes wouldn’t get [such diseases],” she says.
Instead, researchers should concentrate on finding ways to keep the immune
system busy, Fazekas says. She speculates that a new psoriasis vaccine
(see “Shot puts an end to body’s rash behaviour”)
works by mimicking a germ-rich environment.
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Fazekas’s idea is that the immune system restricts the number of its key
fighters, or T cells, that are active to limit the cost of killing invaders.
“The immune system can use an immense amount of energy,” she says.
T cells are switched on by other immune cells called dendritic cells, which
in turn are triggered by invading pathogens. Fazekas and her colleagues have now
shown that this is a two-way conversation. In mice, activated T cells inhibit
dendritic cells, preventing them from switching on other T cells. This feedback
ensures that the immune system does not get overloaded in a mucky,
disease-ridden environment, Fazekas suggests.
In a clean environment, however, dendritic cells are not inhibited, leaving
them highly sensitive. This would make them more likely to inadvertently
stimulate T cells to attack the body’s own proteins and trigger autoimmune
disease. “It is only when nothing else is going on that the immune system starts
to respond to the body’s own tissues,” Fazekas says.
Fasekas’s theory stems from attempts to understand a curious paradox: when
she and Woon-Puay Koh, also of the Centenary Institute, treated mice so that
they had only a tenth as many T cells as normal, the animals’ immune systems
became more active rather than less. The mice also developed colitis, an
autoimmune bowel disease.
Fazekas thinks that reducing the number of T cells reduces the number of such
cells that can inhibit the dendritic cells, mimicking an ultra-clean
environment. “It’s a very nice theory,” says Richard Boyd of Monash University
in Melbourne. “We know in the thymus there is two-way talk between T cells and
non-T cells, so there is a precedent.”
