Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice

Palma, Joann P.; Lee, Hee Gu; Mohindru, Mani; Kang, Bong Su; Canto, Mauro Dal; Miller, Stephen D.; Kim, Byung S.

doi:10.1016/s0165-5728(01)00293-4

Cited by 30 publications

(47 citation statements)

References 48 publications

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“…3 to 5). The importance of CD8 ϩ T cells in viral resolution is consistent with previous reports of mice with resistant backgrounds (38,45,47). However, it is also possible that deficiencies in virus-specific CD4 ϩ T-cell and antibody responses in P1-Tg mice contribute to the lack of viral clearance, as these immune responses play a role in TMEV clearance from the CNS, especially during the early stages of viral infection (6,22,40,43).…”

Section: Most Epitopes Recognized By Cns-infiltrating Cd4supporting

confidence: 88%

“…Despite numerous studies, the relationship between viral persistence and the pathogenesis of demyelinating disease remains unclear. The removal of either B or T cells from resistant mice results in elevated viral persistence but increased demyelination with/without marginal clinical symptoms or encephalitis, a different neurological disease often without demyelination (6,22,41,42,45,47). These results imply that demyelination and/or the development of demyelinating disease is tightly associated with viral persistence.…”

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confidence: 99%

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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

Myoung¹,

Bahk²,

Kang³

et al. 2008

J Virol

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Section: Most Epitopes Recognized By Cns-infiltrating Cd4supporting

confidence: 88%

mentioning

confidence: 99%

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

Myoung¹,

Bahk²,

Kang³

et al. 2008

J Virol

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“…ϩ T cell effector function as well as in MHC class I Ag presentation display enhanced susceptibility to disease (22,(51)(52)(53)(54). In contrast, other studies maintain a pathogenic role for CD8 ϩ T cells based on the lack of clinical signs of disease after infection of mice lacking molecules involved in CD8 ϩ T cell function (55,56).…”

Section: Discussionmentioning

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

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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.

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“…npg regulate some immune responses [13][14][15]. The main mechanism for this effect is believed to be that CTLs can rapidly eliminate dendritic cells (DC) loaded with specific antigen, in a perforin-dependent manner, to restrict the immune response.…”

Section: Discussionmentioning

confidence: 99%

“…The patients would die within a few months of the onset of symptoms if not treated appropriately. Extensive studies have revealed that perforin can downregulate T cells-mediated immune responses in lupus [14] and Theiler's virus-induced demyelinating disease [15]. In addition to its cytotoxic function in CD8 + T cells, these results suggest that perforin may play other roles in T cells function during different types of immune responses, and that it is more than just an effector molecule in the immune response [16].…”

Section: Introductionmentioning

confidence: 98%

Novel function of perforin in negatively regulating CD4+ T cell activation by affecting calcium signaling

Huang

et al. 2009

Cell Res

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Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic T lymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4 + T cell function remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4 + T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell proliferation and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD4 + T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFAT1. Our results indicate that perforin plays a negative role in regulating CD4 + T cell activation and immune response by affecting TCR-dependent Ca 2+ signaling.

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Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice

Cited by 30 publications

References 48 publications

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

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

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

Novel function of perforin in negatively regulating CD4+ T cell activation by affecting calcium signaling

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