THE immune system may be far more flexible than we thought. The cells that coordinate the activities of the immune system appear to change their identity in response to environmental cues. This discovery might one day make it possible to reprogram the immune system to prevent autoimmune diseases and stop the body rejecting a transplant.
For years immune cells called T-helper (Th) cells were assumed to come in just two types 鈥� Th1 cells, which help evict viruses and bacteria from their host cells, and Th2 cells, primed to fight parasites and bacteria in blood and other body fluids as well as taking on allergens. Then things got complicated with the discovery of two new classes of Th cells: regulatory T-cells (T-regs), which dampen the immune system, and Th17 cells, involved in triggering inflammation and autoimmunity.
But when John O鈥橲hea, Bill Paul and Keji Zhao of the National Institutes of 午夜福利1000集合 in Bethesda, Maryland, and colleagues studied all four types of T-helper cells from mice, they found hints that these cells could switch roles or phenotypes in response to environmental cues.
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To test this, they exposed mouse T-regs to signalling molecules associated with a Th1 response and found that the T-regs did indeed behave like Th1 cells (Immunity, ). 鈥淭hey turned out to be more flexible than was envisioned,鈥� says O鈥橲hea.
In another study, Casey Weaver and colleagues at the University of Alabama in Birmingham showed that TH17 cells can also morph into Th1-like cells if they are deprived of a signalling molecule called TGF-beta (Immunity, ).
If T-helper cells are just as flexible inside our bodies, it could affect how diseases are treated. For instance, the right molecules would turn off harmful immune responses, such as those that cause autoimmune diseases like rheumatoid arthritis. 鈥淚f we understood the rules for changing the phenotypes of these cells in humans, that might be very helpful,鈥� says O鈥橲hea.
鈥淭he right molecules could turn off harmful immune responses, such as those that cause arthritis鈥�
However, there may be serious implications for immunotherapy trials in which T-regs are injected into people with autoimmune disease to dampen their immune response. At Northwick Park Hospital in London in March 2006, six men were left fighting for their lives after injections with a drug designed to activate T-regs.
Preliminary evidence from a study in mice suggests that T-regs might turn into Th17-like cells under certain conditions, which would actually exacerbate the illness by ramping up the autoimmune response. 鈥淚t is at least reason for pause and consideration,鈥� says O鈥橲hea.
The new discoveries make it imperative for doctors to keep a close eye on patients undergoing such immunotherapy, in case the immune cells swap identities and cause the immune system to work in unexpected, even harmful ways.
If TH1 cells are equally flexible, vaccines may not work as they are intended, says Christopher Wilson of the University of Washington in Seattle. For instance, if a vaccine against a virus triggers a TH1 response but the TH1 cells then change their identity for some reason, 鈥渢he pathogen might yet subvert the protection induced by the vaccine鈥�, he says.