Costimulatory pathways in multiple sclerosis

Costimulatory molecules can be categorized based either on their functional attributes or on their structure. The costimulatory molecules discussed in this review will be divided into (1) positive costimulatory pathways: promoting T cell activation, survival and/or differentiation; (2) negative costimulatory pathways:antagonizing TCR signalling and suppressing T cell activation; (3) as third group we will discuss the members of the TIM family, a rather “new” family of cell surface molecules involved in the regulation of T cell differentiation and Treg function. Costimulatory pathways have a critical role in the regulation of alloreactivity.  A complex network of positive and negative pathways regulates T cell responses.  Blocking costimulation improves allograft survival in rodents and non-human primates. The costimulation blocker belatacept is being developed as immunosuppressive drug in renal transplantation.

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