Abstract
Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders.
Highlights
Multiple Sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), is the most common cause of non-traumatic neurological disability among young adults in the Western Hemisphere [1]
In addition to DIS, a definitive diagnosis has traditionally required the occurrence of a second clinical exacerbation following the presenting episode or the subsequent emergence of a new lesion visualized by magnetic resonance imaging (MRI) (dissemination in time (DIT))
An independent laboratory found that IFNγ/IL-17-co-expressing CD4+ T cells are abundant in post-mortem MS lesions, and that lymphocytes obtained from relapsing MS patients have a propensity to expand into IFNγ/IL-17 co-producers [93]
Summary
Multiple Sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), is the most common cause of non-traumatic neurological disability among young adults in the Western Hemisphere [1]. The cellular sources of OCBs are presumably meningeal B cells and plasma cells, which have been observed to be clustered with T cells in loose aggregates or lymphoid follicles, in relapsing and progressive MS specimens, respectively [9,10]. By secreting chemokines, such as CXCL12 and CXCL13, and growth factors, such as B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), activated microglia and astrocytes could create a CNS microenvironment in people with MS that is conducive to the accumulation and survival of memory B cells and plasma cells [11]. They could act as antigens presenting cells to encephalitogenic T cells, secrete pro-inflammatory and neurotoxic factors, and/or drive the development of meningeal follicles [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
