The interplay between the immune and central nervous systems in neuronal injury.

Once perceived as a region of limited immune activity, the CNS is now known to be an important site of immune interactions. Activated T cells can infiltrate the blood-brain barrier where they accumulate and proliferate in response to antigen restimulation. These leukocytes express proinflammatory cytokines that help in activating microglia and other immune cells. A profound inflammatory response ensues, which can lead to axonal injury and demyelination. In contrast, other T cells can be neuroprotective. CD4(+) Th2 cells secrete anti-inflammatory cytokines and can elicit the production of bioactive neurotrophins from CNS glia. In addition, neurons themselves can contribute to immune system regulation by being targets of neurotoxic T cells or by altering T-cell activity, including the generation of regulatory T cells. The interplay between components of the immune system and CNS contributes both to healthy brain function and to the pathogenesis of neurodegenerative diseases such as multiple sclerosis.