As it stands, the main therapy for autoimmune diseases involves suppressing inflammation by inhibiting immune cells with anti-inflammatory medications and steroids. While they temporarily relieve symptoms, these drugs can hamper the immune system at the same time and leave patients susceptible to infections.
That’s why scientists are looking to develop a new type of treatment that targets the autoimmune and inflammatory immune cells without compromising the immune system's function.
New research, highlighted in Science Translational Medicine, details how researchers developed special T-cells that can destroy disease-causing immune cells without eliminating good immune cells needed to protect against infections.
Reprogramming the Immune System
The research was led by Shimpei Kasagi of the National Institutes of Health (NIH), who figured out how to produce regulatory T-cells, or Tregs, that can treat autoimmune diseases. The researchers created a suppressed immune environment in mice with either experimental autoimmune encephalomyelitis or non-obese diabetes using an immune-regulating molecule called TGF-beta. Then they injected autoantigenic-peptides into the animals; these peptides are molecules that produce specific Tregs and resulted in antigen-specific T-cell differentiation.
The Tregs then stopped inflammatory responses by traveling into the tissues and organs of the mice. In essence, the researchers reprogrammed the immune system with the Tregs.
The scientists found that the newly generated Tregs not only stopped the autoimmune disease, but the animals were able to stay disease-free long after stopping the peptide injection.
The key for this treatment is the introduction of autoantigen-specific Tregs. The procedures aim to reprogram the native T-cells to differentiate into immunosuppressive regulatory T-cells, not to pro-inflammatory effector T-cells, said Dr. WanJun Chen, one of the researchers with the NIH. Once reprogrammed, these autoantigen-specific Tregs regenerate, which is probably why the mice in the study continued to experience disease remission after the treatment.
It still needs to be confirmed if more peptides would need to be administered for long-term remission, Chen said.
“The long and dramatic effectiveness and duration of the suppression of the autoimmune diseases is better than we expected,” Chen said.
As a result of the treatment, the mice had normal immune system defense when exposed to bacterial antigens.
Looking to the Future
What’s next for this methodology? The researchers say they want to assess how the Tregs work in animals with other autoimmune diseases, such as arthritis, before performing clinical trials in humans.
In theory, the protocol could be applied to other types of autoimmune diseases in mice—and, ultimately, in humans—as long as researchers identify one or more autoantigens specific to the particular disease.
“Maybe MS and type I diabetes are the diseases we should explore first,” Chen said in a statement.
For now, Chen said it provides a big step to reach the “Holy Grail” of immunology research—that is, how to target immune cells without weakening a patient’s immune system.