T‐ and B‐cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis

Abstract

The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody-mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re-evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expressed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, inducing severe EAE in both rodents and primates. In rat and marmoset models of MOG-induced EAE demyelination is antibody-dependent and reproduces the immunopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG-specific B cell response, although if present this will enhance disease severity and demyelination. Clinical studies indicate that autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG-specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summary of our current understanding of MOG as a target autoantigen in EAE and MS, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual.

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

“…This might be explained by the fact that MBP-EAE pathogenetically differs from the MOG-induced variant as it mainly represents the autoimmune T-cell response. 9,47 We are aware that we cannot fully exclude changes in subtypes or activation patterns of immune cells in our model. On the other hand, the results from our histopathological evaluation correlate well with the VEP recordings in which we observed no improvement in ON function following Epo treatment.…”

“…[7][8][9] In a previous study, we demonstrated that in this animal model neuritis of the optic nerve (ON) provokes apoptotic retinal ganglion cell (RGC) death and thereby leads to a severe impairment of visual functions. 10 Recently, we showed that high-dose methylprednisolone treatment, the standard therapy of acute MS relapses, increases neurodegeneration in MOG-EAE by inhibiting an endogenous neuroprotective pathway in RGCs.…”

Rafts in oligodendrocytes: Evidence and structure–function relationship

“…MOG is an integral myelin-specific protein, which is localized in the outer lamella of the myelin sheath and therefore exposed to the extracellular environment. Although MOG is only a minor component of the myelin membrane (0.01-0.05 % of the total myelin protein content), it induces severe EAE after administration to both rodents and primates (Iglesias et al, 2001;Johns and Bernard, 1999). Furthermore, injection of mAbs against MOG into rodents causes extensive myelin destruction in situ (Linington et al, 1988).…”

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

“…MOG is localized at the outer surface of the CNS myelin sheath where it can be targeted by demyelinating autoantibody responses directed against its extracellular N-terminal Ig-like domain (MOG Igd ) (23,24). In MOG-induced EAE, this demyelinating Ab response acts synergistically with an encephalitogenic MOG-specific T cell response to reproduce the inflammatory demyelinating pathology of MS (21,22).…”