Intervention studies of cotton steaming to reduce biological effects of cotton dust.

Abstract

Most therapeutic approaches to control multiple sclerosis (MS) target autoimmune effector cells via broad spectrum immunosuppression. In contrast to this approach we have recently described a therapeutic intervention for the MS model experimental autoimmune encephalomyelitis (EAE) that selectively eliminates encephalitogenic T cells, while sparing protective naive and memory T cell responses. Here we report the mechanistic pathway by which our selective therapy acts. The specificity of action that targets encephalitogenic T cell is through the action of the drug, etoposide, which acts by targeting the double stranded break repair mechanism associated with highly activated T cells. In combination with differential expression of Bcl-2 family member leads to the preferential deletion of effector T cells over memory and naive T cells clearance. Based on our understanding of etoposide-mediated clearance of encephalitogenic T cells we expanded our findings to include other genotoxic and non-genotoxic agents that synergize to afford more specific and less toxic means of controlling autoimmunity. This study further defines the mechanism for the selective clearance of self-reactive T cells by establishing a mechanistic understanding and rational approach to the use of agents that target autoreactive T cells in vivo and result in novel and enhanced therapy for autoimmune diseases.