Multiple Sclerosis: Early Warnings in the Immune System

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Multiple sclerosis (MS) is a chronic inflammatory disease in which the immune system attacks the central nervous system. This impairs the transmission of signals between the brain and body and can lead to deficits in vision, motor control, sensation, and cognitive impairment. The causes of MS are still incompletely understood. In a study of identical twins, a team led by PD Dr Lisa Ann Gerdes (Institute of Clinical Neuroimmunology at LMU University Hospital, Biomedical Center and SyNergy cluster of excellence) has shown that a type of immune cells, CD8-positive T cells, play a role in the early stages of the disease.

Although it is known that CD8 T cells occur in inflammatory areas in the brains of MS patients, it was unclear what role they play in the disease: Are they a mere by-product or active facilitators of inflammation? And what prompts their entry from the blood into the central nervous system? The LMU team has now investigated these questions with the help of this unique patient cohort, comparing the CD8 T cells of monozygotic twin pairs, of which one twin suffers from MS while the other is asymptomatic.

The twin cohort allows the analysis of high-risk patients

Genes and the environment partially determine who might get MS. Monozygotic twins offer a unique insight into this, as these factors are largely identical. As the healthy twin has an elevated risk (up to 25%) of also developing MS, they allow researchers to investigate the early stages of MS. “It’s a unique opportunity to investigate high-risk patients before the disease manifests,” says Vladyslav Kavaka, first author of the paper.

Using innovative methods such as combining single-cell RNA sequencing and T cell receptor analyses, the researchers analysed CD8 T cells from blood and cerebrospinal fluid (CSF) samples taken from the twin pairs. Their results show that CD8 T cells occur with the same specific changes in MS patients and people with early signs of the disease. In addition, they exhibit increased migration ability, promote inflammation and show activation markers. “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, where we encounter the same cells,” explains Dr. Eduardo Beltrán, one of the lead authors. The researchers also found this cell type in the brain tissue of MS patients, which indicates lasting changes in the CNS.

Early stages of the disease are already visible

Intriguingly, the same CD8 T cells did not only occur in people with MS. They were also present in those who did not yet exhibit any symptoms but in whom there were other signs of inflammation without symptoms being evident. Thus, these cells could be earlier facilitators of MS before symptoms arise.

According to the authors, these findings could open new therapeutic avenues that involve influencing CD8 T cells to slow or prevent the progress of MS. In addition, CD8 T cells could be used to develop new diagnostic methods that allow MS to be detected early enough to halt irreversible nerve damage.

V. Kavaka et al.: Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis. Science Immunology