ReviewUsing EAE to better understand principles of immune function and autoimmune pathology
Section snippets
Clinical history of MS
Aspects of the pathology of MS were described as early as the mid-1800's with Cruveilhier in particular noting the existence of MS lesions in the CNS [6]. However, the first comprehensive description of the disease was provided in the 1860's by Charcot, who emphasized the requirement for multiple distinct attacks in the proper characterization of MS [7], [8]. Indeed, MS must be distinguished clinically from acute disseminated encephalomyelitis (ADEM), an idiopathic condition of acute central
Relapsing EAE (R-EAE) in the SJL/J strain
EAE may be induced in mice through either active immunization with protein or peptide, or by passive transfer of encephalitogenic T cells. In either case, the relevant immunogen is derived from self-CNS proteins such as myelin basic protein (MBP), proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG). Immunization of SJL/J mice with the immunodominant epitope of PLP (PLP139–151) induces a relapsing-remitting disease course [12], while disease induced by the immunodominant MOG
EAE models of active MOG peptide immunization on the C57BL/6J background
The relative ease of transgenesis and genetic ablation in the C57BL/6J (B6) strain has made it the de facto strain of choice for studying immune and autoimmune responses [32]. Thus, there was great interest in developing models of EAE in H-2b-restricted animals, as this would facilitate the study of how individual genes and molecular pathways affect disease progression. In an important initial study, Ben-Nun and colleagues [33] studied the ability of multiple MOG-derived peptides to induce EAE
2D2 transgenic mice
Much as had been the case for EAE research in the SJL/J strain, there was an emerging need to generate TcR transgenic models of MOG-driven EAE that could allow one to study the contribution of specific genes to T cell driven CNS autoimmunity. While peptide immunization of T cell or bone marrow-chimeric mice can yield important insights [16], such an approach is cumbersome. Our group has developed a class II-restricted TcR transgenic model to study MOG35–55-driven EAE. An epitope-reactive T cell
Role of the Th17 subset in EAE
Over 20 years ago, Mosmann and Coffman first described two subtypes of T helper cells that could be discriminated on the basis of cytokine production. T helper 1 (Th1) cells were shown to produce interferon (IFN)γ [59], while Th2 cells were described as producing interleukin (IL)-3, IL-4, IL-5 and IL-13 [59], [60], [61]. The Th1/Th2 paradigm soon came to dominate our understanding of effector CD4+ T cell responses. Th1 cells were shown to clear intracellular pathogens, while Th2 cells were
Concluding remarks
Dr. Abul Abbas, to whom this volume is dedicated, has worked for the last three decades in the field of autoimmunity and tolerance. He has made seminal contributions to our understanding of cytokine balance (Th1/Th2 paradigm), costimulatory molecules (CD28/CTLA-4) and regulatory T cell function (Foxp3+). He has also helped generate multiple transgenic models of autoimmunity using model antigens. Abul has an incredible talent for synthesizing complex information in a succinct and simple manner,
Declarations
The authors declare no conflict of interest. M.R. is supported by the EMD Serono, Canada and MS Research and Training Network Transitional Career Development Award from the MSSOC and the Multiple Sclerosis Scientific Research Foundation, as well as by the CHU de Québec. This work was funded by grants from the U.S. National Institutes of Health to V.K.K (NS045937, AI073748, NS038037).
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