Protective and detrimental immunity: lessons from stiff person syndrome and multiple sclerosis

Background - The immune system may attack the brain and cause inflammatory disorders like multiple sclerosis (MS). On the other hand, the immune system may protect and support neurons. Methods -There are two obstacles to study this paradox in humans. First, the target antigens in many human central nervous system (CNS) disorders are unknown. Second, it is often difficult to separate pathogenic from protective events, as well as primary from secondary phenomena. Idiopathic stiff person syndrome (SPS) circumvents the first obstacle, because most patients secrete antibodies against glutamic acid decarboxylase (GAD) 65. The immune response against glatiramer acetate (GA) may circumvent the second obstacle. Migration of activated T helper cells to the intrathecal compartment could be a common denominator in GA treatment and SPS. Results - We here discuss recent results on T cells in MS and SPS, showing that GAD65-specific and GA-reactive lymphocytes in the cerebrospinal fluid are not a simple reflection of those in blood. Conclusion - The rules and mechanisms governing T cell selection and maintenance in the CNS may provide a key to the understanding of protective and detrimental aspects of CNS immunity.