This project builds on previous findings from my group that newly diagnosed, treatment-naive people with multiple sclerosis have fewer memory T cells compared to age- and sex-matched healthy controls. Preliminary data suggest that this reduction may be due to a decreased proliferative capacity of T cells under homeostatic conditions in multiple sclerosis, indicating potential T cell dysfunction. In addition, we have observed elevated levels of senescence-associated cytokines in the plasma of people with multiple sclerosis, which might be indicative of a senescent and/or exhausted T cell phenotype. We hypothesized that chronic exposure to myelin and/or Epstein-Barr virus peptides in multiple sclerosis may induce a state of T cell senescence and/or exhaustion, which might contribute to multiple sclerosis activity and progression.

The AIM of this project is to:

• study whether the immune dysfunction observed in people with multiple sclerosis is associated with a state of cellular senescence and/or exhaustion.
• correlate the inflammatory environment present in multiple sclerosis with T cell function and phenotype, including their senescent/exhausted state.
• evaluate T cell responses to Epstein-Barr virus and myelin peptides within the inflammatory environment associated with multiple sclerosis.