The Potential for Immunospecific Therapy in Multiple Sclerosis Based on Identification of Driver Clones of the Disease.

ABSTRACT

The autoimmune disease multiple sclerosis (MS) is driven by T cells that are reactive to self-antigens of the brain and spinal cord. Many drugs have been developed to treat MS, but we believe that immune-specific targeting of pathogenic T cells may be a better approach for treatment. This type of therapy identifies specific components of the self-reactive T-cell repertoire that would undergo similar natural selection criteria as those found in driver genes in cancer genesis. In the context of autoimmunity, we propose that a focused subpopulation of T cells "drive" disease and could be found in higher frequency and become over-represented during disease induction and subsequent MS relapses. In addition, identification of other key signatures of driver T cells is important. One such marker could be interleukin (IL)-17- producing T cells. Here, we discuss the use of experimental autoimmune encephalomyelitis (EAE) animal models (that mimic many pathologic mechanisms involved in MS) to identify possible driver clones of this autoimmunity within the set of T cells expressing the IL-17 cytokine. EAE can be induced by myelin injection-associated proteins in adjuvants. The disease model in the Swiss/Jackson laboratory mouse strain represents the most common form of MS in humans relapsing remitting MS. Finally, we discuss the concept of using IL-17 as a marker for pathogenic T cells, combined with identifying their T-cell receptor V repertoire, which could provide targeted approaches designed to neutralize driver T cells for MS immunotherapy.