A recent study carried out at the Dana-Farber Cancer Institute has uncovered a new strategy to successfully prevent rheumatoid arthritis in a mouse model, promising better treatment of this and other autoimmune disorders in the future.
About 1.5 million Americans are afflicted with rheumatoid arthritis, which is caused by inflammation and typically results in painfully deformed fingers and hands. Drugs are usually given to reduce inflammation and slow down disease; for example, to block chemicals called cytokines which actually attack tissues and joints. However, these drugs are not optimal and can have serious side effects.
The Dana-Farber research team found that infusing a specific type of immune cell, called CD8+ regulatory T-cells, into arthritis-prone mice shuts down the inflammation responsible for damaging tissues and joints in rheumatoid arthritis.
Normally, the human immune system attacks and destroys infections, viruses, parasites, and other foreign ‘invaders’. In autoimmune diseases, the immune system turns mistakenly inward to attack the individual's own healthy cells and tissues, because it doesn’t recognize them as part of the same body.
Typically, autoimmune attacks begin with overactive immune fighters, called T follicular ‘helper’ cells that mistakenly and aggressively respond to ‘self’ markers on healthy cells. These T helper cells become chronically overactivated, triggering a continuous attack by antibodies on the body's own tissues and joints and damaging them.
Previous research has shown that CD8+ regulatory T-cells turn off the immune response when it's no longer needed, for example after the body has repelled viral or bacterial invaders. This is why the Dana-Farber research team tested regulatory T-cells to see if they could kill off harmful T helper cells, triggering arthritis in their mouse model.
Their innovative approach worked well when regulatory T-cell infusions were given at the same time that mice were injected with a protein that triggered the arthritis-causing autoimmune reaction. In fact, even when regulatory T-cell infusions were administered (in combination with low doses of methotrexate) weeks after disease was triggered, they were able to significantly slow down arthritis development.
Promisingly, this novel strategy even worked when the scientists found a way to increase the pool of CD8+ regulatory T-cells already present in their test mice, rather than infusing them from outside.
Next, the researchers plan to test this approach in mice with human immune cells that provoke the autoimmune response, along with studying practical methods they could use some day for human therapy.