Principles in Effector T Cells

Neurological autoimmunity is a mistargeted immune response of the central or peripheral nervous system. Multiple sclerosis (MS) is a neuroimmune disease involving autoreactive T cells in the central nervous system (CNS). In MS, immune cells infiltrate the CNS and attack the myelin sheaths, leading to demyelination, axonal damage, and neurological disabilities (Baxter, Nat Rev Immunol 7(11):904–912 (2007); Hauser and Oksenberg, Neuron 52(1):61–76 (2006); Trapp and Nave, Annu Rev Neurosci 31:247–269 (2008)). The role of CD4+ T helper cells in MS pathology has been widely studied using animal models such as experimental autoimmune encephalomyelitis (EAE). Classically, the dysregulation of the balance between pro-inflammatory CD4+ T helper 1 (Th1) cells and anti-inflammatory Th2 cells plays an important role in MS development. Recent studies have provided evidence that interleukin (IL)-17-expressing Th17 cells are essential for disease pathogenesis. Furthermore, CD8+ T cells are predominantly observed at human MS lesion sites. However, their functions in this disease remain poorly understood. In this chapter, we summarize the roles of effector T cells in neuroimmune diseases, focusing on findings from studies involving EAE and individuals with MS. Excess inflammatory responses can induce demyelination and progressive neuronal degeneration, leading to functional disabilities. We also discuss approaches to modulate the immune system and attenuate neuronal degeneration as therapeutic targets for MS.