Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

Fritzsching, Benedikt; Haas, Jürgen; König, F.; Kamtchouing, Pièrre; Fritzsching, Eva; Pöschl, Johannes; Krammer, Peter H.; Brück, Wolfgang; Suri‐Payer, Elisabeth; Wildemann, Brigitte

doi:10.1371/journal.pone.0017988

Cited by 95 publications

(75 citation statements)

References 45 publications

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“…Concentrations of CD4+ CD25+ FOXP3+ Treg cells are low in MS lesions; however, their numbers in peripheral blood and CSF are increased 37. This finding suggests that patients with MS do not have an insufficient number of Treg cells; rather, this regulatory cell population is dysfunctional 37.…”

Section: T-cell (Cd4+ and Cd8+) Functionmentioning

confidence: 95%

Immunomodulatory activity of interferon‐beta

Kasper

Reder

2014

Ann Clin Transl Neurol

113

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Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these interactions is to shift cytokine networks in favor of an anti-inflammatory effect. The pleiotropic mechanism of action may be a critical factor in determining the efficacy of interferon-beta in MS. This review will focus on select immunological mechanisms that are influenced by this type I cytokine.

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Section: T-cell (Cd4+ and Cd8+) Functionmentioning

confidence: 95%

Immunomodulatory activity of interferon‐beta

Kasper

Reder

2014

Ann Clin Transl Neurol

113

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“…+ T-cells that play a crucial role in maintaining self-tolerance and preventing autoimmune diseases (Sakaguchi et al 2006;Corsini et al 2011;Fritzsching et al 2011). Therefore, any therapy that leads to an increase in the number and functions of T reg cells could be considered as a potential candidate for use in the treatment of MS.…”

Section: Foxp3mentioning

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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“…T regulatory (Treg) cells play an opposite role to Th1 and Th17 cells. Tregs accumulate in the CNS of EAE animals, especially during the resolution phase (McGeachy et al, 2005), and impaired frequency and function of Treg cells have been reported in CNS lesions of MS patients (Fritzsching et al, 2011). The transfer of CD4 + CD25 + Treg cells protects animals from EAE (McGeachy et al, 2005), in part in an IL-10-dependent manner (Zhang et al, 2004), and Treg depletion exacerbates EAE, increasing IL-6, IL-17 and IFNc production (Reddy et al, 2005).…”

Section: Introductionmentioning

confidence: 99%