Roles of Effector T Cells in Neurological Autoimmunity

Abstract

Neurological autoimmunity is a mistargeted immune response to the central or peripheral nervous system. Multiple sclerosis (MS) is one of many neuroimmune diseases involving autoreactive T cells in the central nervous systems (CNS). In MS, immune cells infiltrate the CNS and attack myelin sheaths, leading to demyelination, axonal damage, and neurological disabilities (Trapp and Nave, Annu Rev Neurosci 31:247–269, 2008; Hauser and Oksenberg, Neuron 52:61–76, 2006; Baxter, Nat Rev Immunol 7:904–912, 2007). The role of CD4+ T helper cells in MS pathology has been widely studied using animal models such as experimental autoimmune encephalomyelitis (EAE). Classically, it is considered that 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. More recent studies have provided evidence that interleukin (IL)-17-expressing Th17 cells are also essential for disease pathogenesis. Furthermore, CD8+ T cells are predominantly observed in human MS lesion sites. However, their functions in this disease are understudied. 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 a therapeutic target for MS.