Emerging concepts in autoimmune encephalomyelitis beyond the CD4/TH1 paradigm

Batoulis, Helena; Addicks, Klaus; Küerten, Stefanie

doi:10.1016/j.aanat.2010.06.006

Cited by 65 publications

(69 citation statements)

References 201 publications

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“…It has been documented that, in addition to increased number of autoimmune T-cells, the decreased numbers and dysfunction of regulatory T (T reg )-cells are involved in the pathogenesis of MS (Batoulis et al 2010). T reg cells have been defined as CD4 + CD25 +…”

Section: Introductionmentioning

confidence: 99%

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Nosratabadi

Rastin

Sankian

et al. 2015

Journal of Immunotoxicology

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Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and antiinflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG 35-55 -induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG 35-55 and then administered different doses of hyperforin or HPE postimmunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (T reg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased T reg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of T reg cell and could eventually be considered as a potential candidate for use in the treatment of MS. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Nosratabadi

Rastin

Sankian

et al. 2015

Journal of Immunotoxicology

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“…It is a heterogeneous disease, and clinical presentation ranges from a benign-type MS with little or no progression following initial onset to a primary progressive MS characterized by a relatively acute and severe clinical decline. The most common form, relapsing-remitting MS, accounts for 85% of cases and manifests as a series of discrete episodes separated by complete or partial remission (1,2 (2,5).…”

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confidence: 99%

Cutting Edge: Mast Cells Regulate Disease Severity in a Relapsing–Remitting Model of Multiple Sclerosis

Sayed

Walker

Brown

2011

The Journal of Immunology

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Mast cells (MCs) exert a significant pathologic influence on disease severity in C57BL/6 (B6) strain-dependent experimental allergic encephalomyelitis (EAE), a model of primary progressive multiple sclerosis (MS). However, relapsing–remitting MS, which is modeled in SJL mice, is the more prevalent form. Given genetically determined heterogeneity in numbers and responsiveness of MCs from various strains of mice, we asked whether these cells also influence this more clinically relevant MS model using SJL-KitW/W-v mice. Similar to the commercially available WBB6F1-KitW/W-v mice, SJL-KitW/W-v mice are MC-deficient, anemic, and neutropenic and have normal T cell compartments. They exhibit significantly reduced disease severity, but retain the relapsing–remitting course, a phenotype reversed by selective MC reconstitution. These data confirm that MC influence is not confined to an isolated model of EAE and reveal a new system to study the effects of MC heterogeneity on relapsing–remitting EAE and other SJL strain-specific diseases.

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“…Nevertheless, we still observed changes in the expression of key regulators of T effector subsets in 15-wk-old Grb2 fl/fl CD4cre tg mice that show normal T cell numbers. However, the changes in effector T cells did not render the Grb2 fl/fl CD4cre tg mice more susceptible in the inflammation-based EAE model that is primarily driven by Th1 and Th17 cells (21,22). In contrast, Grb2 fl/fl CD4cre tg mice developed less severe EAE-associated symptoms than controls and had higher numbers of Tregs.…”

Section: Discussionmentioning

confidence: 89%

“…This leads to inflammation in the CNS. Freund's adjuvant is used to boost the immune response against myelin oligodendrocyte glycoprotein (MOG); by using this immunization protocol, the disease is primarily driven by Th1 and Th17 cells (21,22).…”

mentioning

confidence: 99%

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

Radtke

Lacher

Szumilas

et al. 2016

The Journal of Immunology

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The small adaptor protein growth factor receptor–bound protein 2 (Grb2) modulates and integrates signals from receptors on cellular surfaces in inner signaling pathways. In murine T cells, Grb2 is crucial for amplification of TCR signaling. T cell–specific Grb2fl/fl Lckcretg Grb2-deficient mice show reduced T cell numbers due to impaired negative and positive selection. In this study, we found that T cell numbers in Grb2fl/fl CD4cretg mice were normal in the thymus and were only slightly affected in the periphery. Ex vivo analysis of CD4+ Th cell populations revealed an increased amount of Th1 cells within the CD4+ population of Grb2fl/fl CD4cretg mice. Additionally, Grb2-deficient T cells showed a greater potential to differentiate into Th17 cells in vitro. To test whether these changes in Th cell differentiation potential rendered Grb2fl/fl CD4cretg mice more prone to inflammatory diseases, we used the murine Th1 cell– and Th17 cell–driven model of experimental autoimmune encephalomyelitis (EAE). In contrast to our expectations, Grb2fl/fl CD4cretg mice developed a milder form of EAE. The impaired EAE disease can be explained by the reduced proliferation rate of Grb2-deficient CD4+ T cells upon stimulation with IL-2 or upon activation by allogeneic dendritic cells, because the activation of T cells by dendritic cells and the subsequent T cell proliferation are known to be crucial factors for the induction of EAE. In summary, Grb2-deficient T cells show defects in T cell development, increased Th1 and Th17 cell differentiation capacities, and impaired proliferation after activation by dendritic cells, which likely reduce the clinical symptoms of EAE.

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Emerging concepts in autoimmune encephalomyelitis beyond the CD4/TH1 paradigm

Cited by 65 publications

References 201 publications

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Cutting Edge: Mast Cells Regulate Disease Severity in a Relapsing–Remitting Model of Multiple Sclerosis

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

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