In a recent study published in Nature, researchers prevented T cells from causing the normal autoimmune damage that comes with spinal cord injury, sparing neurons and successfully aiding recovery in mouse models.
In spinal cord injury, the wound site attracts a whole host of peripheral immune cells, including T cells, which result in both beneficial and deleterious effects. Notably, antigen-presenting cells activate CD4+ T cells to release cytokines, ultimately leading to neuroinflammation and tissue destruction. This neuroinflammation is notably most pronounced during the acute phase of spinal cord injury. The problem is that these same T cells have a neuroprotective effect initially, only later developing autoimmunity and attacking the injury site.
Using single cell RNA sequencing, the researchers found that CD4+ T cell clones in mice showed antigen specificity towards self-peptides of myelin and neuronal proteins. Self-peptides have been implicated in a wide range of autoimmune conditions.
Using mRNA techniques, the researchers edited the T cell receptor, so that they shut off after a few days. In mouse models of spinal cord injury, they showed notable neuroprotective efficacy, partly as a result of modulating myeloid cells via interferon-γ.
Their findings provided insights into the mechanisms behind the neuroprotective function of injury-responsive T cells. This will help pave the way for the future development of T cell therapies for central nervous system injuries, and perhaps treatments for neurodegenerative diseases such as Alzheimer’s.
