In autoimmune diseases, immune cells mistakenly identify the body's own tissues as foreign and mount an inappropriate attack. But by genetically modifying the cells that make the erroneous identification, scientists at Queensland University, Australia, have been able to stop them misbehaving.

The feat has only been achieved in the test tube so far, but the researchers are now using the approach to try to produce a vaccine against rheumatoid arthritis.

Re-educating the immune system is not a new idea, says Ranjeny Thomas, who led the study. A similar approach has been used to tackle an opposite problem, when the immune system fails to identify cancerous cells.

"What's different is that this is the first time it has been possible to suppress an existing response, once the immune system has started down a deleterious pathway," says Ranjeny.

"They are nice pre-clinical experiments," says rheumatoid arthritis expert Ravinder Nath Maini, at Imperial College London. But he cautions: "We are very far away from any application."

Engulfed intruders
 

The immune cells that alert our bodies to foreign material, or mistakenly to our own tissue, are called dendritic cells. Engulfing the intruders sets off a chain of events that enables the dendritic cells to activate another set of immune cells known as T cells. In turn, these generate the immune response, enabling our body to attack the intruder.

However, when the scientists knocked out the gene for one of the dendritic cell's proteins, called RelB, the dendritic cell was no longer able to put another protein, called CD40, onto its surface. Without CD40 on its surface, the dendritic cells inactivated the T cells instead of activating them, thereby suppressing the immune response.

In rheumatoid arthritis, the immune system misidentifies the joints as foreign proteins and eats away at the cartilage and damages the underlying bone.

Although it is not known what molecule the dendritic cells are recognising, there are a number of candidates, says Thomas. She is now testing them with her manipulated dendritic cells to see if she can develop a vaccine that will prevent rheumatoid arthritis.

For a vaccine, dendritic cells taken from a person's blood would be modified by knocking out RelB and then exposing them to the molecule triggering the autoimmune disease. This would specifically prime the cells to that disease and stop them from activating the immune response.

"Past vaccines for arthritis failed because they were not targeting the correct pathway," she says. "But this is a very potent form of suppression and we could have a vaccine within five to 10 years."

Journal reference: Immunity (vol 18, p 155)

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