Pathogenesis of Multiple Sclerosis—The Immune Diathesis and the Role of Viruses

Allen, Ingrid V.; Brankin, Brenda

doi:10.1097/00005072-199303000-00001

Cited by 95 publications

(45 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A large number of infiltrating immune cells such as T cells and macrophages are found in the brain and spinal cord of patients with MS and are thought to be responsible for the demyelination of neurons found primarily in the white matter of the CNS (1,2). Although the cause of MS has not been elucidated, epidemiological studies suggest a viral etiology for this disease (3,4). When the first cases of MS were discovered it was noted that women were affected much more than men.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Fuller

Kang

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Multiple sclerosis is an immune-mediated disease of the CNS and shows a sex-biased distribution in which 60–75% of all cases are female. A mouse model of multiple sclerosis, Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease, also displays a gender bias. However, in the C57L/J strain of mice, males are susceptible to disease whereas females are completely resistant. In this study we determined the gender differences in the TMEV-specific immune response, which may be responsible for the gender bias in clinical disease. Our data clearly demonstrate that female C57L/J mice induce significantly higher levels of TMEV-specific neutralizing Ab as well as a stronger peripheral T cell response throughout the course of viral infection. In contrast, male mice have a higher level of TMEV-specific CD4+ and CD8+ T cell infiltration into the CNS as well as viral persistence. These results suggest that a higher level of the initial antiviral immune response in female mice may be able to effectively clear virus from the periphery and CNS and therefore prevent further disease manifestations. Male mice in contrast do not mount as effective an immune response, thereby allowing for eventual viral persistence in the CNS and continuous T cell expansion leading to clinical symptoms.

show abstract

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Fuller

Kang

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Furthermore, the various immunological and genetic factors that affect disease outcome in mice closely parallel those associated with the development of MS in humans (21). Combined with a suspected viral etiology for MS (1,10,46), these similarities make TMEV a relevant infectious model for the study of this human autoimmune disease.…”

mentioning

confidence: 97%

“…Although the etiology of multiple sclerosis (MS) remains unknown, epidemiological studies and animal models have supported a potential role for viruses as causative agents of demyelination (1,7,10). One such virus is Theiler's murine encephalomyelitis virus (TMEV), a common enteric mouse picornavirus.…”

mentioning

confidence: 99%

Capsid-Specific Cytotoxic T Lymphocytes Recognize Three Distinct H-2D^b-Restricted Regions of the BeAn Strain of Theiler's Virus and Exhibit Different Cytokine Profiles

Lyman

Lee

Kang

et al. 2002

J Virol

View full text Add to dashboard Cite

The role of virus-specific cytotoxic T lymphocytes (CTL) inBased on cytokine profiles, CTL specific for these subdominant epitopes are Tc2, in contrast to CTL for the immunodominant epitope, which are of the Tc1 type. Interestingly, CTL function towards both of these subdominant epitopes is restricted by the H-2D molecule, despite the fact that these epitopes bind both H-2K and H-2D molecules. This skewing toward an H-2D b -restricted response may confer resistance to TMEVinduced demyelinating disease, which is known to be associated with the H-2D genetic locus.

show abstract

“…Although the etiology of MS is not clarified yet, epidemiological studies and investigations with experimental animal models have supported a potential role for viruses as the environmental trigger in disease induction (Allen and Brankin, 1993). Thus, a similar demyelinating disease induced by a virus could be one of the most attractive animal models in the study of the pathogenesis of MS. Theiler's murine encephalomyelitis viruses (TMEV), members of the genus Cardiovirus in the family of Picornaviridae, are natural enteric pathogens that cause CNS disease in mice (Pevear et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease

Takizawa

Kaneyama

Tsugane

et al. 2014

Journal of Neuroimmunology

View full text Add to dashboard Cite

Programmed death-1 (PD-1) belongs to the CD28 family of co-stimulatory and co-inhibitory molecules and regulates adaptive immunity. This molecule induces the development of regulatory T cells, T cell tolerance, or apoptosis. We examined the role of PD-1 pathway in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) mice. Up-regulation of PD-1 and PD-1 ligand-1 (PD-L1) mRNA expression in bone marrow-derived dendritic cells were induced by TMEV infection in vitro. Furthermore, PD-1 and PD-L1 mRNA expression was increased in the spinal cords of the TMEV-infected mice in vivo. Treatment with a blocking monoclonal antibody (mAb) against PD-1, especially during the effector phase, resulted in significant deterioration of the TMEV-IDD both clinically and histologically. Flow cytometric analysis revealed a dramatically increase of CD4 + T cells producing Th1 cytokines such as IFN-γ and TNF-α in the spinal cord of anti-PD-1 mAbtreated mice. These results indicate that the PD-1 pathway plays a pivotal regulatory role in the development of TMEV-IDD.

show abstract

Pathogenesis of Multiple Sclerosis—The Immune Diathesis and the Role of Viruses

Cited by 95 publications

References 0 publications

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Capsid-Specific Cytotoxic T Lymphocytes Recognize Three Distinct H-2D^b-Restricted Regions of the BeAn Strain of Theiler's Virus and Exhibit Different Cytokine Profiles

Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease

Contact Info

Product

Resources

About

Pathogenesis of Multiple Sclerosis—The Immune Diathesis and the Role of Viruses

Cited by 95 publications

References 0 publications

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Gender Bias in Theiler’s Virus-Induced Demyelinating Disease Correlates with the Level of Antiviral Immune Responses

Capsid-Specific Cytotoxic T Lymphocytes Recognize Three Distinct H-2Db-Restricted Regions of the BeAn Strain of Theiler's Virus and Exhibit Different Cytokine Profiles

Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease

Contact Info

Product

Resources

About

Capsid-Specific Cytotoxic T Lymphocytes Recognize Three Distinct H-2D^b-Restricted Regions of the BeAn Strain of Theiler's Virus and Exhibit Different Cytokine Profiles