Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Evonuk, Kirsten S.; Moseley, Carson E.; Doyle, Ryan E.; Weaver, Casey T.; DeSilva, Tara M.

There are a number of ways in which treatments can affect immune cells and the CNS, each with the end result of reducing severity of EAE symptoms. Therefore, it is necessary to use flow cytometric analysis and immunohistochemistry to look at how immune cells are affected in the periphery and CNS, whether immune cells have entered the CNS, and how the CNS reacts to treatment. While flow cytometric analysis of the spinal cord can determine how many cells have entered the CNS at a given time, one cannot determine that this effect is due to reduced immune cell trafficking unless proliferation of immune cells is unaffected in the spleen. It is therefore necessary to analyze both peripheral and CNS tissue and determine what results mean mechanistically when both tissues are compared. It is also possible for immune cell activity profiles to be altered by treatment, for example having a switch in a pathogenic helper T cell-heavy profile to a regulatory T cell-heavy profile. Looking at markers for different cell types and comparing percent expression between treated and untreated animals is therefore also an important consideration. An emerging concept in MS research suggests that B cells play an important role in autoimmune demyelination. This is based on studies showing that B cells are necessary for the reactivation of T cells 20 . This concept is supported by the success of treatments such as rituximab, an antibody against CD20 expressed on the surface of B cells 21, 22 . As demonstrated by the success of the monoclonal antibody ocrelizumab in clinical trials, drugs targeting different epitopes of CD20 may improve the efficacy of B cell-targeted therapeutics 23 .