New twin study implicates certain T-cells in early MS inflammation
Early activation, migration into brain of CD8 T-cells tied to MS onset
By studying pairs of identical twins, researchers have identified a population of immune cells whose early activation and migration into the brain might contribute to multiple sclerosis (MS) onset.
MS patients showed an altered profile of a population of immune cells called CD8 T-cells in the blood relative to their identical twins without the disease or any signs of neuroinflammation. But in twins without MS who did show evidence of early inflammation — a possible indicator that they may eventually develop the disease — similar alterations in CD8 T-cells were observed.
“Collectively, these findings shed light on the central proinflammatory role of disease-associated CD8+ T cells in … MS … offering possible targets for monitoring and treating immune dysregulation in MS,” the researchers wrote, noting that the data “provide detailed insights into the characteristic molecular alterations underpinning the disease.”
The study, “Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis,” was published in Science Immunology.
Investigating early MS inflammation in the brain
MS is characterized by the immune system’s mistaken attack on healthy components of the nervous system, leading to nerve cell damage and degeneration. Several immune cell types have been implicated in this process, and researchers are still working to understand which ones are byproducts of existing inflammation and which are actual drivers of the disease.
Among them are CD8 T-cells, a pro-inflammatory group of immune cells found at high levels within MS brain lesions. Still, it’s not well understood how these cells make their way from the bloodstream and into the brain in MS in large numbers.
Both genetic and environmental factors are thought to influence the development of MS. But the great variability seen among these factors in patients has made it difficult for researchers to identify early immunological changes specific to MS. That’s where the idea for a twin study comes into play.
One approach to learning more about the factors contributing to MS development while eliminating confounding genetic and environmental factors from the equation is to study pairs of identical twins, where one twin has MS and the other doesn’t.
[The MS TWIN study is] a unique opportunity to investigate high-risk patients before the disease manifests.
Research has shown that if one twin has MS, the identical sibling has a 25% risk of also developing the condition during his or her lifetime. Scientists can leverage this, and examine data from the seemingly healthy twin who may already have some very early signs of MS.
“It’s a unique opportunity to investigate high-risk patients before the disease manifests,” Vladyslav Kavaka, a doctoral student at the Ludwig Maximillan University (LMU) of Munich and the study’s first author, said in a university news story.
The MS TWIN study involves such pairs of identical twins. Among those without MS, some don’t show any signs of brain inflammation, while some have subclinical indicators of inflammation that still don’t fulfill the criteria for an MS diagnosis. The individuals with subclinical indicators may be considered to be at a very early, or prodromal, stage of disease.
Previous work in the MS TWIN study indicated that CD8 T-cells were activated and expanding in the cerebrospinal fluid, or CSF — the fluid surrounding the brain and spinal cord — in both the twins with MS and those with subclinical neuroinflammation.
Study examined CD8 T-cells in 12 pairs of identical twins
In the new study, the researchers sought to further profile these cells and learn more about how they become dysregulated and migrate to the brain. The team, from LMU and other institutions in Germany, examined the profile of CD8 T-cells in the blood and CSF of 12 twin pairs from the MS TWIN study.
The results showed that in the blood and CSF samples of MS patients, CD8 T-cells exhibited gene activity alterations consistent with an activated, pro-inflammatory, and migratory state, which were not observed in their healthy twins with no neuroinflammation. Signs of altered energy metabolism were also observed.
Importantly, according to the researchers, a similar profile was seen in cells taken from twins with subclinical neuroinflammation, indicating that early CD8 T-cell alterations may already be present before overt disease onset.
Analyses of previously collected data from the brain tissue of another group of MS patients indicated that the changes in CD8 T-cells observed in the blood and CSF were also evident in the brain.
“These properties show that these CD8 T cells are migratory in the blood and are already embarking on their journey to the central nervous system [brain and spinal cord], where we encounter the same cells,” said Eduardo Beltrán, PhD, one of the study’s senior authors who was a researcher at LMU at the time the work was conducted.
Ultimately, the scientists believe their findings position CD8 T-cells as a promising therapeutic target for slowing MS progression. They could also be used to facilitate early disease detection, allowing treatment to start before significant nervous system damage has accumulated.
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