In vivo administration of interleukin-2 protects susceptible mice from Theiler's virus persistence

Larsson-Sciard, Eva-Lotta; Dethlefs, Sven; Brahic, Michel

doi:10.1128/jvi.71.1.797-799.1997

Cited by 23 publications

(12 citation statements)

References 22 publications

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“…CTL appear to play an important role in the pathogenesis of TMEV-induced disease. Several lines of evidence are supporting the significance of CD8 ϩ CTL in clearing TMEV, including the following: (i) resistance to demyelinating disease in B6 mice is determined by the H-2D b locus (22); (ii) passive transfer of CD8 ϩ T lymphocytes from resistant TMEV-infected BALB/cByJ mice to susceptible BALB/cAnNcr animals protected the latter against demyelinating disease but only when the transfer of the cells was carried out early enough to allow clearance of TMEV; and (iii) DBA/2 mice can be protected from TMEV-induced demyelinating disease by in vivo administration of interleukin-2 (IL-2), a growth factor for T cells that may act by recruiting virus-specific CTL (226).…”

Section: Cytotoxic T Lymphocytesmentioning

confidence: 99%

Theiler's Virus Infection: a Model for Multiple Sclerosis

Chang²,

et al. 2004

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Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans

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Section: Cytotoxic T Lymphocytesmentioning

confidence: 99%

Theiler's Virus Infection: a Model for Multiple Sclerosis

Chang²,

et al. 2004

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“…In contrast, in SJL/J mice, CTL activity appears around day 7 post-inoculation and remains at low levels for several months (S. Dethlefs, personal communication). Interestingly, the administration of IL-2-secreting cells to SJL/J mice prior to inoculation significantly increases the number of virus-specific CTL precursors and renders the recipients resistant (51).…”

Section: Cytolytic T Cellsmentioning

confidence: 99%

The infection of mouse by Theiler's virus: from genetics to immunology

Monteyne

Bureau

Brahic

1997

Immunological Reviews

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Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter of the spinal cord with chronic inflammation and demyelination. This late disease is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility to persistent infection and demyelination. Resistant strains clear the infection after the acute encephalomyelitis. This observation is the basis of genetic studies which we used as a thread for this review. The H-2D locus has a major effect on susceptibility. The H-2Db gene is involved in a fast and intense CTL response which confers resistance. The Tcrb locus is also implicated, although there is no proof that the susceptibility gene in this region codes for the T-cell receptor. A complete screen of the genome uncovered the role of the Ifng locus and led to the demonstration that IFN-gamma limits viral spread in the white matter. The roles of NK cells and B cells in limiting the infection are discussed. CD4+ T cells participate both in protection against the infection and in demyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene.

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“…More recently, researchers have begun to unveil the beneficial role that CD8 ϩ T cells may have in resolving infection and immune protection. An early and abundant TMEV-specific CD8 ϩ T-cell response is critical in determining the balance between viral persistence or resolution of infection (6,22,30).…”

mentioning

confidence: 99%

Protection against Lethal Encephalomyocarditis Virus Infection in the Absence of Serum-Neutralizing Antibodies

Neal

Splitter

1998

J Virol

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Although the ability of serum-neutralizing antibodies to protect against picornavirus infection is well established, the contribution of cell-mediated immunity to protection is uncertain. Using major histocompatibility complex class II-deficient (RHAβ−/−) mice, which are unable to mediate CD4+ T-lymphocyte-dependent humoral responses, we demonstrated antibody-independent protection against lethal encephalomyocarditis virus (EMCV) infection in the natural host. The majority of RHAβ−/− mice inoculated with 104 PFU of attenuated Mengo virus (vMC24) resolved infection and were resistant to lethal challenge with the highly virulent, serotypically identical cardiovirus, EMCV. Protection in these mice was in the absence of detectable serum-neutralizing antibodies. Depletion of CD8+T lymphocytes prior to lethal EMCV challenge ablated protection in vMC24-immunized RHAβ−/− mice. The CD8+ T-lymphocyte-dependent protection observed in vivo may, in part, be the result of cytotoxic T-lymphocyte (CTL) activity, as CD8+ T splenocytes exhibited in vitro cytolysis of EMCV-infected targets. The existence of virus-specific CD8+T-lymphocyte memory in these mice was demonstrated by increased expression of cell surface activation markers CD25, CD69, CD71, and CTLA-4 following antigen-specific reactivation in vitro. Although recall response in vMC24-immunized RHAβ−/− mice was intact and effectual shortly after immunization, protection abated over time, as only 3 of 10 vMC24-immunized RHAβ−/− mice survived when rechallenged 90 days later. The present study demonstrating CD8+ T-lymphocyte-dependent protection in the absence of serum-neutralizing antibodies, coupled with our previous results indicating that vMC24-specific CD4+ T lymphocytes confer protection against lethal EMCV in the absence of prophylactic antibodies, suggests the existence of nonhumoral protective mechanisms against picornavirus infections.

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In vivo administration of interleukin-2 protects susceptible mice from Theiler's virus persistence

Cited by 23 publications

References 22 publications

Theiler's Virus Infection: a Model for Multiple Sclerosis

Theiler's Virus Infection: a Model for Multiple Sclerosis

The infection of mouse by Theiler's virus: from genetics to immunology

Protection against Lethal Encephalomyocarditis Virus Infection in the Absence of Serum-Neutralizing Antibodies

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