Using EAE to better understand principles of immune function and autoimmune pathology

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which myelin becomes the target of attack by autoreactive T cells. The immune components of the disease are recapitulated in mice using the experimental autoimmune encephalomyelitis (EAE) model. EAE is classically induced by the immunization of mice with encephalitogenic antigens derived from CNS proteins such as proteolipid protein (PLP), myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Immunization of susceptible mouse strains with therse antigens will induce autoreactive inflammatory T cell infiltration of the CNS. More recently, the advent of clonal T cell receptor transgenic mice has led to the development of adoptive transfer protocols in which myelin-specific T cells may induce disease upon transfer into naïve recipient animals. When used in concert with gene knockout strains, these protocols are powerful tools by which to dissect the molecular pathways that promote inflammatory T cells responses in the central nervous system (CNS). Further, myelin-antigen-specific transgenic T cells may be cultured in vitro under a variety of conditions prior to adoptive transfer, allowing one to study the effects of soluble factors or pharmacologic compounds on T cell pathogenicity. In this review, we describe many of the existing models of EAE, and discuss the contributions that use of these models has made in understanding both T helper cell differentiation and the function of inhibitory T cell receptors. We focus on the the step-by-step elucidation of the network of signals required for T helper 17 (Th17) cell differentiation, as well as the molecular dissection of the Tim-3 negative regulatory signaling pathway in Th1 cells.

Liposome-Based Immunotherapy Against Autoimmune Diseases: Therapeutic Effect on Multiple Sclerosis

“…It is induced by the administration of myelin antigens. The most frequent EAE model used is C57BL/6 mice injected with the MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] peptide [16,17], and it has been the major tool to understand the mechanism involved in MS pathogenesis, as well as to test therapies for the human disease. To determine the effect of a therapy in EAE, three different approaches can be used: preventive (before immunization), preclinical (postimmunization) and therapeutic (after the onset of the disease) [17].…”

Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation

“…With a prevalence of 2.5 million patients worldwide, MS is the most frequent autoimmune disorder of the CNS. Studies in humans and mice demonstrated a prominent role of CD4 T cells in the pathogenesis of autoimmune demyelinating diseases, in particular of T-bet1/IFNγ-positive Th1 cells and RORγt/IL-17-positive Th17 cells (3)(4)(5)(6). Current therapeutic concepts for the treatment of MS include i.v.…”

Grb2 Is Important for T Cell Development, Th Cell Differentiation, and Induction of Experimental Autoimmune Encephalomyelitis

“…Experimental autoimmune encephalomyelitis (EAE) is an animal model for the early inflammatory phase of human multiple sclerosis, but it is also useful to deepen the understanding of Th cell functions in a disease situation in vivo (19,20). To induce EAE, an immune reaction is initiated against a part of the myelin that surrounds nerve cells.…”