Anticapsid Immunity Level, Not Viral Persistence Level, Correlates with the Progression of Theiler's Virus-Induced Demyelinating Disease in Viral P1-Transgenic Mice

Myoung, Jinjong; Bahk, Young Yil; Kang, Hyunil; Canto, Mauro C. Dal; Kim, Byung S.

doi:10.1128/jvi.02442-07

Cited by 24 publications

(34 citation statements)

References 59 publications

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“…Therefore, epitope-specific cytotoxic CD8 ϩ T cells may similarly play a protective or pathogenic role depending on the type and/or reactivity of epitopes. We previously demonstrated that the level of the VP3 159-166 -specific CD8 ϩ T cell response in susceptible SJL mice is inversely correlated with viral persistence in P1-transgenic (P1-Tg) SJL mice (40), highlighting the importance of VP3 159-166 -specific CD8 ϩ T cells in limiting the viral load in vivo. Surprisingly, however, higher viral persistence in P1-Tg mice did not lead to a higher disease incidence and/or severity.…”

Section: Discussionmentioning

confidence: 99%

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Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Myoung

Kang

Hou

et al. 2012

J Virol

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Theiler's virus-induced demyelinating disease has been extensively investigated as a model for persistent viral infection and multiple sclerosis (MS).؉ T cells exhibited high functional avidity for gamma interferon production, whereas VP3 173-181 -specific CD8 ؉ T cells showed low avidity. To our knowledge, this is the first report indicating that the induction of the IL-17-producing CD8 ؉ T cell type is largely epitope specific and that this specificity apparently plays a differential role in the pathogenicity of virus-induced demyelinating disease. These results strongly advocate for the careful consideration of CD8 ؉ T cell-mediated intervention of virus-induced inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

“…ϩ T cell responses to subdominant epitopes (40). Interestingly, P1-transgenic SJL mice lacking CD8 ϩ T cell responses to the predominant epitope develop less severe delayed clinical disease.…”

Section: T Has Been Well Established That Virus-specific Cd8mentioning

confidence: 99%

Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Myoung

Kang

Hou

et al. 2012

J Virol

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“…This shows that administration of anti-PD-1 mAb did not affect the viral load in the CNS, despite the deteriorated disease development. There are increasing evidences that viral persistence levels are not associated with the development of TMEV-IDD (Myoung et al, 2008;Jin et al, 2009). Viral persistence alone may not be sufficient to induce the disease and that the level of T cell immunity to viral capsid epitopes may be critical for the development of demyelinating disease in SJL mice (Myoung, Bahk, 2008).…”

Section: Discussionmentioning

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

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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.

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“…Therefore, clonal expansion of certain CD8 ϩ T cells may be associated with the pathogenesis of demyelinating diseases. However, B6 mice, which are resistant to TMEV-induced demyelinating disease, induce strong CD8 ϩ T-cell responses to a single predominant epitope (VP2 121-130 ), i.e., Ն70% of CNSinfiltrating CD8 ϩ T cells (41,42). These CD8 ϩ T cells result in effective viral clearance yet remain at a low level in the CNS more than 120 days postinfection (dpi) without detectable pathology (42).…”

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confidence: 99%

“…However, B6 mice, which are resistant to TMEV-induced demyelinating disease, induce strong CD8 ϩ T-cell responses to a single predominant epitope (VP2 121-130 ), i.e., Ն70% of CNSinfiltrating CD8 ϩ T cells (41,42). These CD8 ϩ T cells result in effective viral clearance yet remain at a low level in the CNS more than 120 days postinfection (dpi) without detectable pathology (42). This inconsistency led us to investigate the shape and quality of the T-cell receptor (TCR) repertoire accumulating in the CNSs of B6 mice.…”

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confidence: 99%

Predominant Clonal Accumulation of CD8⁺T Cells with Moderate Avidity in the Central Nervous Systems of Theiler's Virus-Infected C57BL/6 Mice

Kang

Kim

2010

J Virol

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Induction of antigen-specific CD8؉ T cells bearing a high-avidity T-cell receptor (TCR) is thought to be an important factor in antiviral and antitumor immune responses. However, the relationship between TCR diversity and functional avidity of epitope-specific CD8 ؉ T cells accumulating in the central nervous system (CNS) during viral infection is unknown. Hence, analysis of T-cell diversity at the clonal level is important to understand the fate and function of virus-specific CD8 ؉ T cells. In this study, we examined the V␤ diversity and avidity of CD8 ؉ T cells specific to the predominant epitope (VP2 121-130 ) of Theiler's murine encephalomyelitis virus. We found that V␤6 ؉ CD8 ؉ T cells, associated with epitope specificity, predominantly expanded in the CNS during viral infection. Further investigations of antigen-specific V␤6 ؉ CD8 ؉ T cells by CDR3 spectratyping and sequencing indicated that distinct T-cell clonotypes are preferentially increased in the CNS compared to the periphery. Among the epitope-specific V␤6 ؉ CD8 ؉ T cells, MGX-J␤1.1 motif-bearing cells, which could be found at a high precursor frequency in naïve mice, were expanded in the CNS and tightly associated with gamma interferon production. These T cells displayed moderate avidity for the cognate epitope rather than the high avidity normally observed in memory/effector T cells. Therefore, our findings provide new insights into the CD8 ؉ T-cell repertoire during immune responses to viral infection in the CNS.

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Anticapsid Immunity Level, Not Viral Persistence Level, Correlates with the Progression of Theiler's Virus-Induced Demyelinating Disease in Viral P1-Transgenic Mice

Cited by 24 publications

References 59 publications

Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

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

Predominant Clonal Accumulation of CD8⁺T Cells with Moderate Avidity in the Central Nervous Systems of Theiler's Virus-Infected C57BL/6 Mice

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Anticapsid Immunity Level, Not Viral Persistence Level, Correlates with the Progression of Theiler's Virus-Induced Demyelinating Disease in Viral P1-Transgenic Mice

Cited by 24 publications

References 59 publications

Epitope-Specific CD8+T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Epitope-Specific CD8+T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

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

Predominant Clonal Accumulation of CD8+T Cells with Moderate Avidity in the Central Nervous Systems of Theiler's Virus-Infected C57BL/6 Mice

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Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Epitope-Specific CD8⁺T Cells Play a Differential Pathogenic Role in the Development of a Viral Disease Model for Multiple Sclerosis

Predominant Clonal Accumulation of CD8⁺T Cells with Moderate Avidity in the Central Nervous Systems of Theiler's Virus-Infected C57BL/6 Mice