Induction of a Multiple Sclerosis-Like Disease in Mice with an Immunodominant Epitope of Myelin Oligodendrocyte Glycoprotein

Slavin, Anthony; Ewing, Christine; Liu, Junliang; Ichikawa, Motoki; Slavin, John; Bernard, Carole

doi:10.3109/08916939809003872

Cited by 128 publications

(101 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most functional knockout mice are bred onto the C57BL/6 strain, which is highly susceptible to EAE induced by immunization with MOG (39). It is clear that T cells producing Th2 cytokines in this model are nonencephalitogenic and also to confer protection against EAE.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Treatment Down-Regulates TNF-α Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice

Ito¹,

Bebo

Matejuk³

et al. 2001

The Journal of Immunology

245

201

View full text Add to dashboard Cite

A shift toward Th2 cytokine production has been demonstrated during pregnancy and high dose estrogen therapy and is thought to be the primary mechanism by which estrogen suppresses the development of experimental autoimmune encephalomyelitis. However, low dose estrogen treatment is equally protective in the absence of a significant shift in cytokine production. In this study cytokine-deficient mice were treated with estrogen to determine whether a shift in Th2 cytokine production was required for the protective effects of hormone therapy. Estrogen effectively suppressed the development of experimental autoimmune encephalomyelitis in IL-4 and IL-10 knockout mice and in wild type littermate mice with a similar potency of protection. Significant disease suppression was also seen in IFN-γ-deficient mice. The decrease in disease severity was accompanied by a concomitant reduction in the number of proinflammatory cytokine- and chemokine-producing cells in the CNS. Although there was no apparent increase in compensatory Th2 cytokine production in cytokine-deficient mice, there was a profound decrease in the frequency of TNF-α-producing cells in the CNS and the periphery. Therefore, we propose that one mechanism by which estrogen protects females from the development of cell-mediated autoimmunity is through a hormone-dependent regulation of TNF-α production.

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen Treatment Down-Regulates TNF-α Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice

Ito¹,

Bebo

Matejuk³

et al. 2001

The Journal of Immunology

245

201

View full text Add to dashboard Cite

show abstract

“…In C57/Bl6 mice, MOG-induced disease develops around day 15 (Table 1), and the mice undergo an acute phase lasting 10-12 days. Around 50% of the mice develop a persistent chronic disease at the end of the acute phase, which is characterized by a disease grade of 1 or more (20).…”

Section: Methodsmentioning

confidence: 99%

“…CNS tissue samples were obtained on days [13][14][15]20, and 50 after immunization. Fluorescein-labeled cells were counted at ×20 magnification throughout the sections, the total area of the sections was measured, and the number of positive cells was expressed per 100 mm 2 of tissue area.…”

Section: Figurementioning

confidence: 99%

Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis

Issazadeh¹,

Abdallah²,

Chitnis³

et al. 2000

J. Clin. Invest.

View full text Add to dashboard Cite

The mechanisms of chronic disease and recovery from relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, are unknown. Deletion of myelin-specific lymphocytes by apoptosis may play a role in termination of the inflammatory response. One pathway of apoptosis is the passive cell death or "cell death by neglect" pathway, which is under the control of the Bcl family of genes. To investigate the role of passive cell death pathway in EAE, we used mice with transgenic expression of the long form of the bcl-x gene (Bcl-x L ) targeted to the T-cell lineage. We found that mice transgenic for Bcl-x L have an earlier onset and a more chronic form of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 compared with wild-type littermate mice. This was not due to an expanded autoreactive cell repertoire. Primed peripheral lymphocytes from Bcl-x L transgenic mice showed increased proliferation and cytokine production to MOG peptide in vitro compared with lymphocytes from wild-type animals. Immunohistologic studies demonstrated increased cellular infiltrates, immunoglobulin precipitation, and demyelination in the Bcl-x L transgenic central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x L transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x L transgenic mice. Our data indicate that the passive cell death pathway is important in the pathogenesis of chronic EAE. These findings have implications for understanding the pathogenesis of multiple sclerosis and other autoimmune diseases.

show abstract

“…In SJL mice EAE was elicited according to Weinberg [41], using PLP 139-151 (HCLGKWLGHPDKF). In C57BL/6 mice EAE was induced with MOG peptide 35-55 (MEVG-WYRSPFSRVVHLYRNGK) as described by Slavin [42]. Disease was evaluated by determination of body weight and EAE scoring according to Heremans [23].…”

Section: Induction and Analysis Of Eaementioning

confidence: 99%

Development of an anti‐IL‐12 p40 auto‐vaccine: protection in experimental autoimmune encephalomyelitis at the expense of increased sensitivity to infection

et al. 2004

View full text Add to dashboard Cite

IL‐12 and IL‐23, which share the IL‐12 p40 subunit, have been ascribed central roles in many autoimmune disorders. We describe here an anti‐IL‐12 (αIL‐12) auto‐vaccine that potentially blocks both factors in vivo. Immunization of mice with mouse IL‐12 coupled to OVA or Pan DR epitope (PADRE) peptide induced Ab directed against the IL‐12 p40 subunit, which prevented IFN‐γ production in response to IL‐12 administration in vivo. Experimental autoimmune encephalomyelitis, an IL‐23‐dependent disease model, induced in SJL mice with a proteolipid protein (PLP) peptide was almost undetectable after αIL‐12 vaccination. Myelin oligodendrocyte glycoprotein (MOG)‐induced disease in C57BL/6 mice was also significantly inhibited. This protection correlated with inhibited Th1 cytokine responses in vitro and with an increase in the IgG1/IgG2a anti‐PLP Ab balance. Detrimental consequences of αIL‐12 vaccination were evaluated in C57BL/6 mice infected with Leishmania major (L.m.). While delayed‐type hypersensitivity (DTH) suppression and immunoglobulin as well as interleukin production patterns reflected a major shift toward a Th2‐type response, L.m. growth was still significantly retarded as compared to that seen in susceptible BALB/c mice. However, vaccinated animals ultimately failed to control parasite expansion. These results suggest that some chronic autoimmune diseases may benefit from αIL‐12 vaccination at the expense of reduced, but not completely abrogated, cell‐mediated immunity.

show abstract

Induction of a Multiple Sclerosis-Like Disease in Mice with an Immunodominant Epitope of Myelin Oligodendrocyte Glycoprotein

Cited by 128 publications

References 26 publications

Estrogen Treatment Down-Regulates TNF-α Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice

Estrogen Treatment Down-Regulates TNF-α Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice

Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis

Development of an anti‐IL‐12 p40 auto‐vaccine: protection in experimental autoimmune encephalomyelitis at the expense of increased sensitivity to infection

Contact Info

Product

Resources

About