Th17 Phenotype of Auto-Reactive T-Cells in Patients with Relapsing Remitting Multiple Sclerosis

Silva Markovic-Plese, M.D.

University of North Carolina School of Medicine

Funded in September, 2010: $200000 for 3 years
LAY SUMMARY .

LAY SUMMARY

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Identifying specific Immune cell malfunctions in patients with multiple sclerosis

Researchers will characterize initial steps in the development of autoimmunity in patients with multiple sclerosis (MS) and identify potential targets for early treatment.

MS is an inflammatory disease of the central nervous system (CNS, comprising the brain and spinal cord). The body’s immune T cells misidentify CNS cells as foreign and mount a highly specific and sustained attack. While about 20 MS patients have a progressively debilitating course, the other 80 percent have “relapsing-remitting” MS, where symptoms intermittently occur and subside. Even within these two subtypes, patients’ symptoms are highly variable, complicating efforts to determine the efficacy of experimental therapies. Scientists need a better understanding of immune system malfunctions to improve on available therapies. From prior research, the researchers hypothesize that in relapsing-remitting MS, a subset of immune T cells (called Th17 T cells) is easily activated to attack for two reasons: 1) Th17 T cells have receptors that recognize a wide range of “antigens,” that are suspected (correctly or not) as being foreign; and 2) Th17 T cells require few other molecules to stimulate their “attack” signals.   

They will test this hypothesis in cerebrospinal fluid (CSF) from 20 patients with relapsing-remitting MS and 10 “control” participants who have no evidence of CNS inflammatory disease. They will explore three questions: 1) Which antigens trigger this self-destructive immune response in the CNS? 2) How are the Th17 T cells activated and differentiated? And, 3) What percent of immune T cells evolve into this destructive subset?

Significance: By characterizing the subset of immune T cells that drive the autoimmune response in relapsing-remitting MS, the research is anticipated to lead to the identification of immune system targets for developing more effective and safer therapies.