B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis

Kala, Mrinalini; Rhodes, Susan N.; Piao, Wenhua; Shi, Fu‐Dong; Campagnolo, Denise I.; Vollmer, Timothy

doi:10.1016/j.expneurol.2009.10.015

Cited by 97 publications

(95 citation statements)

References 46 publications

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“…20,25 Furthermore, adoptive transfer of B cells from glatiramer acetate-treated mice suppresses EAE compared to those injected with PBS or ovalbumin, indicating that the protective effects of glatiramer acetate against MS may be mediated via B cells. 26 In agreement with these studies, T cell depleted lymphocyte preparations, which contain approximately 70% B cells as determined by FACS analysis, were protective against KA-induced neurotoxicity thus adding further support for B cells playing a protective role against certain neurological disorders.Having established that lymphocyte preparations including T cells depleted cells are neuroprotective and independent of activation state of T cells, we then sought to identify the underlying mechanisms. We confirmed that soluble mediators were responsible for the observed neuroprotection as conditioned media was protective against KA-induced neurotoxicity.…”

supporting

confidence: 74%

supporting

confidence: 74%

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Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Shrestha¹,

Millington

Brewer

et al. 2015

Kathmandu Univ. Med. J.

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BackgroundNeurodegenerative disease is a progressive loss of neurons from the central nervous system (CNS). Various conditions have been implicated for such conditions including ageing, inflammation, stress and genetic predisposition. Recently, studies have linked neurodegeneration with inflammation. Some studies have suggested the harmful effect of immune response while others have argued its neuroprotective role in neurodegeneration of the CNS. However, the precise role of inflammation and immune cells in such condition is still not clear. ObjectiveTo investigate the role of lymphocytes in neurodegeneration of the CNS and determine the underlying mechanism. MethodWe have used 4-7 days old mouse pups (C57Bl6) to prepare organotypic slice cultures which were cultured for 13-15 days prior to experiment. To induced cell death kainic acid was used and considered as an in vitro model for neurodegeneration. Lymphocytes were obtained from peripheral lymph nodes of 5-10 weeks old adult mouse which were used in the current study. Propidium iodide was used as a fluorescent dye to determine cell death in brain slice cultures. ResultLymphocytes do not induce cell death in slice cultures in the absence of any toxic insult whereas, after applying toxic insult to the slice cultures using kainic acid, lymphocytes show neuroprotection against such insult. Similarly, purified nonactivated and purified activated T cells along with T cells depleted lymphocyte preparation also exhibit neuroprotection against kainic acid-induced cell death. We further, have demonstrated that the observed neuroprotection is contactindependent and soluble mediators released from lymphocytes are responsible for the observed neuroprotection. Moreover, our study has revealed that soluble mediators exhibiting neuroprotection act via astrocytes. ConclusionLymphocyte preparations are neuroprotective and the observed neuroprotection is contact-independent. Soluble mediators released from lymphocytes are responsible for the observed neuroprotection. Astrocytes, lymphocytes, neurodegeneration, neuroprotection, t cells Page 133 Original Article KEY WORDS Lymphocyte preparationPeripheral lymph nodes were harvested from C57Bl6 mice (6-10 weeks old) and transferred to complete RPMI 1640 (cRPMI) media containing 10% foetal calf serum and 2mM L-Glutamine. The lymph nodes were triturated and passed through a cell strainer (40µM pore), transferred to a sterile tube and centrifuged at 1400 rpm for five minutes. The pellet was then washed at least two times in culture media and the cells were re-suspended in culture media, counted in the presence of trypan blue to identify viable cells and diluted to 1X10 6 cells per ml, the final concentration used in all experiments. T cells were purified from lymphocyte preparations using magnetic-assorted cell sorting (MACS) and depleting non-T cells using a Pan T Cell Isolation Kit (Miltenyi Biotec, UK) following the manufacturer's instructions. Following T cell isolation, the non-T cell fraction was collected for the ...

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supporting

confidence: 74%

supporting

confidence: 74%

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Shrestha¹,

Millington

Brewer

et al. 2015

Kathmandu Univ. Med. J.

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“…Glatiramer acetate (GA) is a drug safely used in MS patients, and it has been demonstrated that the beneficial effects of GA were abrogated in B celldeficient mice. Furthermore, adoptive transfer of B cells from GA-treated mice inhibited the proliferation of autoreactive T cells as well as the development of Th1 and Th17 cells, but promoted IL-10 production in recipient mice (Kala, Rhodes et al 2010;Begum-Haque, Christy et al 2011). Estrogen, a hormone drug with well established therapeutic effects on MS, was shown to depend on B cells as well.…”

Section: Induction and Expansion Of Breg Cells By Chemical Drugs Usedmentioning

confidence: 98%

“…Some regulatory B cell populations have also been shown to be induced in diverse disease settings and in response to many different exogenous and endogenous stimuli. Toll-like receptor (TLR) signalling via TLR-2, 4 and 9 as well as B cell receptor (BCR) signalling and co-stimulation mediated by CD40, CD80/CD86 or B-cell activating factor (BAFF) has been demonstrated to induce B cells with suppressive activity (Fillatreau, Sweenie et al 2002;Mauri, Gray et al 2003;Blair, Chavez-Rueda et al 2009;Kala, Rhodes et al 2010;Lampropoulou, Calderon-Gomez et al 2010;Yang, Sun et al 2010 (Yanaba, Bouaziz et al 2008). The human equivalent to mouse B10 cells has been identified recently as a small population within peripheral blood CD24 hi CD27 + B cells (Iwata, Matsushita et al 2011).…”

Section: Breg Cell Populations In Mice and Humansmentioning

confidence: 99%

“…Furthermore, adoptive transfer experiments revealed a possible therapeutic potential of isolated regulatory B cells in EAE (Mann, Maresz et al 2007;Matsushita, Yanaba et al 2008;Rafei, Hsieh et al 2009;Kala, Rhodes et al 2010). Considering the extensive use of MS treatments that are dependent on B cell depletion, it seems crucial to define this dual role of B cells in the progression of disease.…”

Section: Multiple Sclerosismentioning

confidence: 99%

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Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

Sattler¹,

Vlugt²,

Hussaarts³

et al. 2012

Recent Advances in Immunology to Target Cancer, Inflammation and Infections

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The Effect of Glatiramer Acetate Therapy on Functional Properties of B Cells From Patients With Relapsing-Remitting Multiple Sclerosis

et al. 2014

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IMPORTANCEThis study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS).OBJECTIVE To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS Twenty-two patients with MS who were receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study.EXPOSURES Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES B-cell phenotype and proliferation and immunoglobulin and cytokine secretion.RESULTS A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate.CONCLUSIONS AND RELEVANCE Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.

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B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis

Cited by 97 publications

References 46 publications

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

The Effect of Glatiramer Acetate Therapy on Functional Properties of B Cells From Patients With Relapsing-Remitting Multiple Sclerosis

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