Experimental Autoimmune Encephalomyelitis (EAE) Induced by Antigen Pulsed Dendritic Cells in the C57BL/6 Mouse: Influence of Injection Route

Aghdami, Nasser; Gharibdoost, Farhad; Moazzeni, Seyed Mohammad

doi:10.1538/expanim.57.45

Cited by 19 publications

(18 citation statements)

References 46 publications

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“…52 In the present study, intravenous administration of CGRP-transfected cells both in the induction phase and effector phase ameliorated EAON. The finding that EAON is also suppressed by administration in the effector phase suggests that this cell therapy may be effective even when given after clinical onset of the disease.…”

Section: Discussionsupporting

confidence: 50%

Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene

Matsuda

Kezuka

Nishiyama

et al. 2012

Investigative Ophthalmology & Visual Science

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PURPOSE. Calcitonin gene-related peptide (CGRP) exhibits prominent anti-inflammatory actions. We examined whether CGRP-transfected dendritic cells (DC) prevent the development of experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalomyelitis (EAE). METHODS.A human CGRP-expressing plasmid was constructed, and used to transfect C57BL/6 mouse bone marrow-derived matured DC (mDC) by electroporation methods. Transfection efficiency was 50% with 80% cell viability. C57BL/6 mice were immunized with myelo-oligodendrocyte glycoprotein 35-55, and injected intravenously with CGRP-expressing mDC (CGRP gene-transfected group) or mock-transfected mDC (mocktransfected group) at the induction or effector phase. EAE was diagnosed clinically and EAON was assessed histopathologically. Delayed hypersensitivity was measured. Supernatants of spleen cell cultures were assayed for cytokines using ELISA.þ fraction in spleen cells was analyzed using flow cytometry.RESULTS. For gene therapy in the induction phase, EAE developed in 50% of mice in the CGRP-transfected group compared with 80% in the mock-transfected group, and the mean pathological score for EAON was 1 in the CGRPtransfected group compared with 2 in the mock-transfected group (P < 0.05). For gene therapy in the effector phase, the mean EAE clinical score (1.5 vs. 3.0) and mean EAON pathological score (1.0 vs. 2.0) were both lower in the CGRP-transfected group compared with the mock-transfected group (P < 0.05). Delayed hypersensitivity was suppressed significantly in the CGRP-transfected group. IL-10 production by spleen cells in the CGRP-transfected group increased independent of MOG concentration, compared with the mock-transfected group. Interestingly, the proportion ofþ cells increased significantly (P < 0.05) in the CGRP-transfected group compared with the mock-transfected group.CONCLUSIONS. Gene therapy with CGRP-expressing mDC was effective in suppressing the development of EAON and EAE. (Invest Ophthalmol Vis Sci. 2012;53:5475-5485)

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Section: Discussionsupporting

confidence: 50%

Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene

Matsuda

Kezuka

Nishiyama

et al. 2012

Investigative Ophthalmology & Visual Science

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“…Achieving this as a robust experimental option for the induction of EAE would allow us to probe the molecular requirements for the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the CNS. It is notable, however, that despite some sporadic reports [3-5], this has not as yet been achieved. Classically, the induction of EAE requires the use of complete Freund’s adjuvant (CFA), which contains a range of mycobacterial-derived molecules to trigger DC activation through their pattern-recognition receptors (PRRs).…”

Section: Resultsmentioning

confidence: 94%

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

Mellanby

Cambrook

Turner

et al. 2012

J Neuroinflammation

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BackgroundExperimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4+ T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s). Despite some sporadic reports, however, models of DC-driven EAE have not been widely adopted. We sought to test the feasibility of this approach and whether activation of the DC by toll-like receptor (TLR)-4 ligation was a sufficient stimulus to drive EAE.FindingsHost mice were seeded with myelin basic protein (MBP)-reactive CD4+ T cells and then were injected with DC that could present the relevant MBP peptide which had been exposed to lipopolysaccharide as a TLR-4 agonist. We found that this approach induced robust clinical signs of EAE.ConclusionsDC are sufficient as APC to effectively drive the differentiation of naïve myelin-responsive T cells into autoaggressive effector T cells. TLR-4-stimulation can activate the DC sufficiently to deliver the signals required to drive the pathogenic function of the T cell. These models will allow the dissection of the molecular requirements of the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the central nervous system.

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“…It also has been hypothesized that T-cell-mediated autoimmune reaction is caused by inappropriate presentation of either a self-antigen or an antigen with the capacity to mimic a self-antigen (Weir et al 2002;Aghdami et al 2008).…”

Section: Article In Pressmentioning

confidence: 99%

Cannabinoids and experimental models of multiple sclerosis

Kubajewska

Constantinescu

2010

Immunobiology

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Experimental Autoimmune Encephalomyelitis (EAE) Induced by Antigen Pulsed Dendritic Cells in the C57BL/6 Mouse: Influence of Injection Route

Abstract: Dendritic cells (DCs) are the most potent antigen-presenting cells (APC) of the immune system, and are critically involved in initiation of

Cited by 19 publications

References 46 publications

Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene

Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

Cannabinoids and experimental models of multiple sclerosis

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