Encephalomyelitis Accompanied by Myelin Destruction Experimentally Produced in Monkeys

Rivers, Thomas M.; Schwentker, Francis F.

doi:10.1084/jem.61.5.689

Cited by 396 publications

(89 citation statements)

References 10 publications

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“…The eventual discovery that immune cells caused myelin destruction in a primate model resembling MS3 finally put the field on the right track in the 1930s, and the discovery of an immunoglobulin signature in MS patient cerebrospinal fluid4 – still in use as a diagnostic tool today – firmly cemented the idea that MS is an autoimmune disease. Meanwhile, as medical practice became more advanced after the Second World War, patients were increasingly seen by neurologists specialising in MS, who began to compile long‐term cohorts of patients 5.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide association studies of multiple sclerosis

Cotsapas¹,

Mitrovič

2018

Clin & Trans Imm

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Large‐scale genetic studies of multiple sclerosis have identified over 230 risk effects across the human genome, making it a prototypical common disease with complex genetic architecture. Here, after a brief historical background on the discovery and definition of the disease, we summarise the last fifteen years of genetic discoveries and map out the challenges that remain to translate these findings into an aetiological framework and actionable clinical understanding.

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Section: Introductionmentioning

confidence: 99%

Genome‐wide association studies of multiple sclerosis

Cotsapas¹,

Mitrovič

2018

Clin & Trans Imm

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“…is a chronic inflammatory and demyelinating disease of the CNS believed to be mediated by an autoimmune T cell attack on Ags present in the myelin sheath of the CNS, such as myelin basic protein, proteolipid protein (PLP), or myelin oligodendrocyte glycoprotein (1)(2)(3). To induce the disease, primed, autoreactive T cells must migrate to the CNS and recognize neuroantigens presented by local APCs.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

In Vivo Blockade of Macrophage Migration Inhibitory Factor Ameliorates Acute Experimental Autoimmune Encephalomyelitis by Impairing the Homing of Encephalitogenic T Cells to the Central Nervous System

Denkinger

Kort

et al. 2003

The Journal of Immunology

102

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Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T cell activation. However, its role in the pathogenesis of T cell-mediated autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), has remained unresolved. In this study, we report that anti-MIF Ab treatment of SJL mice with acute EAE improved the disease severity and accelerated the recovery. Furthermore, the anti-MIF treatment impaired the homing of neuroantigen-reactive pathogenic T cells to the CNS in a VCAM-1-dependent fashion. Interestingly, MIF blockade also decreased the clonal size of the neuroantigen-specific Th1 cells and increased their activation threshold. Taken together, the results demonstrate an important role for MIF in the pathogenesis of EAE/multiple sclerosis and suggest that MIF blockade may be a promising new strategy for the treatment of multiple sclerosis.

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“…It is characterized clinically by neurological deficits and histologically by inflammatory infiltrates in the CNS (2)(3)(4). In most animal models of EAE, the disease is induced actively through immunization with myelin proteins such as myelin basic protein (MBP) or proteolipid protein (PLP) in CFA, or passively by transfer of activated neuroantigen-specific T cells.…”

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

Hofstetter

Shive

Forsthuber

2002

The Journal of Immunology

144

110

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Pertussis toxin (PT) has been widely used to facilitate the induction of experimental autoimmune encephalomyelitis (EAE) in rodents. It has been suggested that this microbial product promotes EAE by opening up the blood-brain barrier and thereby facilitates the migration of pathogenic T cells to the CNS. However, PT has other biological effects that could contribute to its activity in EAE, such as enhancing the cytokine production by T cells and induction of lymphocytosis. In this work, we investigated the effects of PT on the pathogenicity, cytokine differentiation, and clonal sizes of neuroantigen-reactive T cells in EAE in mice. Our results show that PT prevented the protection from EAE conferred by injection of PLPp139–151 in IFA and induced high frequencies of peptide-specific Th1 cells and disease. Interestingly, the mice developed EAE despite the simultaneous vigorous clonal expansion of PLPp139–151-specific Th2 cells. The data indicate that the Th2 cells in this model neither were protective against EAE nor promoted the disease. Furthermore, the results suggested that the effects of the toxin on neuroantigen-reactive T cells were promoted by the PT-induced activation of APCs in lymphoid tissues and the CNS. Together, the results suggest that microbial products, such as PT, could contribute to the initiation of autoimmune disease by modulating the interaction between the innate and adaptive immune system in the response to self Ags.

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Encephalomyelitis Accompanied by Myelin Destruction Experimentally Produced in Monkeys

Cited by 396 publications

References 10 publications

Genome‐wide association studies of multiple sclerosis

Genome‐wide association studies of multiple sclerosis

In Vivo Blockade of Macrophage Migration Inhibitory Factor Ameliorates Acute Experimental Autoimmune Encephalomyelitis by Impairing the Homing of Encephalitogenic T Cells to the Central Nervous System

Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells

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