T-Cell Properties Determine Disease Site, Clinical Presentation, and Cellular Pathology of Experimental Autoimmune Encephalomyelitis

Abromson‐Leeman, Sara; Bronson, Rod T.; Luo, Yi; Berman, Michael A.; Leeman, Rebecca J; Leeman, Joshua R.; Dorf, Martin E.

doi:10.1016/s0002-9440(10)63410-4

Cited by 42 publications

(57 citation statements)

References 63 publications

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“…It has been reported that atypical EAE and brain inflammation developed in IFNg À/À or RAG1 À/À IFNg À/À mice, but not in IFNg competent mice. 19,20 By using a passive EAE model, Lees et al 21 showed that adoptive transfer of WT CD4 þ T cells to IFNgR À/À mice elicited brain, but not spinal cord, inflammation. However, the exact targets of IFNg that affect atypical EAE are still elusive.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis

Chen

Wang

Zhang

et al. 2014

The American Journal of Pathology

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The function of blood-brain barrier is often disrupted during the progression of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the molecular mechanism of blood-brain barrier modulation during neuroinflammation remains unclear. Herein, we show that the expression of interferon-γ (IFNγ) receptor on endothelial cells (ECs) protected mice from the brain inflammation during EAE. IFNγ stabilized the integrity of the cerebral endothelium and prevented the infiltration of leukocytes into the brain. Further analysis revealed that IFNγ increased the expression of tight junction proteins zonula occludens protein 1 and occludin, as well as membranous distribution of claudin-5, in brain ECs. Silencing claudin-5 abolished the IFNγ-mediated improvement of EC integrity. Taken together, our results show that IFNγ, a pleiotropic proinflammatory cytokine, stabilizes blood-brain barrier integrity and, therefore, prevents brain inflammation during EAE.

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Section: Discussionmentioning

confidence: 99%

Interferon-γ Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis

Chen

Wang

Zhang

et al. 2014

The American Journal of Pathology

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“…Mice with brain inflammation exhibit distinct clinical signs such as ataxia, proprioception defects, leaning and in some cases an unusual axial-rotary clinical presentation, collectively known as atypical EAE. Additionally, introducing genetic deficiency in IFN-γ signaling into many strains that normally exhibit predominantly spinal cord lesions causes most inflammation to shift to the brain [53-55]. A few other genetically-engineered models have been described that predispose mice to brain inflammation, i.e., overexpression of IL-6 in astrocytes or deletion of SOCS-3 in myeloid cells [56, 57].…”

Section: The Role Of Neutrophils In Shaping Patterns Of Neuroinflamentioning

confidence: 99%

The contribution of neutrophils to CNS autoimmunity

Pierson

Wagner

Goverman

2018

Clinical Immunology

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Multiple sclerosis (MS) is believed to be initiated when myelin-specific T cells infiltrate the central nervous system (CNS), triggering subsequent recruitment of inflammatory leukocytes to the CNS. The contribution of neutrophils to CNS autoimmune disease has been underappreciated, but several studies in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, indicate that neutrophils have an important role in inflammation. Neutrophils are hypothesized to contribute to the pathogenesis of EAE by producing cytokines and promoting breakdown of the blood brain barrier. Neutrophils may also influence the manifestation of EAE by facilitating parenchymal brain inflammation. This review summarizes evidence supporting a functional role for neutrophils in EAE and MS, highlighting the differential regulation of neutrophil recruitment in the brain and spinal cord.

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“…Studies on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, show that the distribution of lesions in the nervous system varies, depending on the Ag and immunization protocol used to induce EAE, and on the MHC and non-MHC genes carried by the animal (3)(4)(5)(6)(7)(8)(9)(10)(11). In MS, the distribution of demyelinated lesions in the CNS can vary from one patient to another, and there is currently no way of predicting where they will develop.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis

Greer

Csurhes

Muller

et al. 2008

The Journal of Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. The numbers of autoimmune T cells and Abs specific for proteins of CNS myelin are increased in the blood in some patients with MS. The aim of this study was to investigate whether there are correlations between the specificity of the autoimmune responses in the blood, the HLA molecules carried by the patient, and the clinical features of MS, because studies on experimental autoimmune encephalomyelitis, an animal model of MS, indicate that autoimmune responses targeting particular myelin proteins and the genetic background of the animal play a role in determining the pattern of lesion distribution. We tested blood T cell immunoreactivity to myelin proteins in 100 MS patients, 70 healthy controls, and 48 patients with other neurological disorders. Forty MS patients had strongly increased T cell reactivity to one or more myelin Ags. In these 40 patients, the most robust correlation was between CD4+ T cell reactivity to myelin proteolipid protein residues 184–209 (PLP184–209) and development of lesions in the brainstem and cerebellum. Furthermore, carriage of HLA-DR4, -DR7, or -DR13 molecules by MS patients correlated with increased blood T cell immunoreactivity to PLP184–209, as well as the development of lesions in the brainstem and cerebellum. Levels of PLP190–209-specific Abs in the blood also correlated with the presence of cerebellar lesions. These findings show that circulating T cells and Abs reactive against specific myelin Ags can correlate with lesion distribution in MS and suggest that they are of pathogenic relevance.

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T-Cell Properties Determine Disease Site, Clinical Presentation, and Cellular Pathology of Experimental Autoimmune Encephalomyelitis

Cited by 42 publications

References 63 publications

Interferon-γ Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis

Interferon-γ Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis

The contribution of neutrophils to CNS autoimmunity

Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis

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