After repeated exposure to a fragment of the myelin protein — the target of autoimmune attack in multiple sclerosis (MS) — immune cells in mice were reprogrammed to be tolerant to myelin, suppressing the immune response associated with the disease, a study revealed.
Researchers showed that in these tolerant T-cells, genes that limit immune responses were enhanced, while genes that activated T-cells were repressed.
These findings support the development of therapies that directly address the underlying autoimmune response in MS patients.
The study, “Chromatin Priming Renders T Cell Tolerance-Associated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes,” was published in the journal Cell Reports.
MS is characterized by the immune system mistakenly attacking myelin — the fatty protective coating that covers nerve fibers. T-cells are a type of immune cell that is involved in the autoimmune attack against the myelin sheath and represents a target for MS treatments.
The process of T-cell activation against an antigen — molecules capable of stimulating an immune response — is tightly regulated and depends on multiple signaling pathways to ensure an appropriate immune response.
A recent review analysis demonstrated that T-cell activation could be suppressed by repeated exposure to an antigen, leading to so-called T-cell tolerance against that antigen. This represents a type of immunotherapy with the potential to desensitize the immune system.
Understanding the mechanism of this phenomenon may help researchers find ways to reprogram T-cells to become tolerant and not attack the myelin sheath, which may lead to effective therapies to treat the underlying cause of MS.