A team of scientists at
Boston's Dana-Farber Cancer Institute has developed a new technique to treat
autoimmune diseases such as rheumatoid arthritis. The approach, which is based
on the infusion of cells that regulate immune responses, has been demonstrated
to to be effective in mice, even weeks after the disease was initiated.
Characterized by joint inflammation, rheumatoid arthritis is one of many
different autonomous diseases. It is estimated that 50 million Americans suffer
from autoimmune disorders which also include lupus, type 1 diabetes, multiple
sclerosis and celiac disease. At least 100 different autoimmune diseases have
been identified.
The human immune system normally, attacks and destroys infections, viruses,
parasites, and other foreign "invaders." But in autoimmune disorders, parts of
the immune system attack the body’s healthy cells and tissues. These parts of
the immune system fail to recognize "self" identifying tags on the body's cells.
In this new research, the mice were first injected with a protein that triggered
the arthritis-causing autoimmune reaction. The scientists then infused CD8 T
regulatory, or CD8 Treg cells, which play a key role turning off an immune
response when it’s no longer needed after the body has repelled viral or
bacterial invaders.
The scientists injected peptide antigens to expand the pool of CD8 Tregs in each
mouse, rather than infusing them from outside. They found that CD8 Tregs
recognized and eliminated those parts of the immune system, called CD4 T helper
cells, that mistakenly respond to the “self” markers on healthy cells and become
chronically over-activated, spurring a continuous attack by antibodies on the
body’s tissues.
When combined with methotrexate, a commonly used drug for treating rheumatoid
arthritis, the researchers found it slowed the disease down significantly.
This “upstream”treatment – where a cell is used to block other cells that spur
an attack by antibodies on the body’s tissues – is different from the way
rheumatoid arthritis is currently treated with inflammation-reducing drugs like
corticosterioids. Suxh "downstream" approaches block secreted chemicals called
cytokines which carry out the attacks, but they can also result in severe side
effects like high blood pressure, weight gain and increased risk of infection.
“We found we could almost completely inhibit the disease in this setting," says
Harvey Cantor, MD, chair of the Department of Cancer Immunology and AIDS at
Dana-Farber. "We believe that targeting the CD4 T cells that initiate this
cascade may be a more effective approach to rheumatoid arthritis therapy."
The researchers will now test mice carrying human immune cells that provoke an
autoimmune response. The collagen-induced arthritis in the mice is seen as
similar to rheumatoid arthritis in humans because they share symptoms including
breach of self-tolerance, generation of auto antibodies, inflammatory changes in
multiple joints, and erosion of bone and cartilage.