ROBERT FUJINAMI

..Thus, while slow to be generated these cytoxic cells could participate in viral clearance...

..Defects in the Treg population could be responsible for the large numbers of virus-specific T cells and occurrence of lymphoproliferation and inflammatory autoimmune disease in HAM/TSP patients...

..These mechanisms are discussed in the context of multiple sclerosis, myocarditis, and diabetes, three immune-medicated diseases often linked with virus infections...

..Further research is needed to determine the interactions between neuropsychiatric and immune dysfunction in autism and related disorders...

..It is possible that the type I interferons, via interleukin 12, provide the link between viruses and autoimmunity...

..While MCMV alone caused no CNS disease, control VV-infected mice followed with MCMV developed mild CNS inflammation. Thus, heterologous virus infections can induce CNS pathology...

..The distribution of axonal injury observed during the early phase corresponded to regions where subsequent demyelination occurs during the chronic phase. The results suggest that axonal injury might herald or trigger demyelination...

..Therefore, axonal degeneration plays contrasting roles (beneficial versus detrimental) depending on the initiator driving the disease...

..Intracerebral injection of the clones into naïve mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8+ Tc1 cells could play a pathogenic role in central nervous system inflammation...

..Lymphocytes from pCMVUPLP-vaccinated mice produced interleukin-4, a cytokine lacking in controls. Thus, pCMVUPLP vaccination can modulate the relapse after EAE induction...

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..The effect of in vivo depletion of NKT cells differed depending on the stage of infection, suggesting contrasting roles for NKT cells over the disease course...

..Recent research into this priming and triggering of disease will be discussed in relation to an animal model for MS...

..Thus, CD1d-restricted NKT cells may play a protective role in TMEV-induced neurological disease by alteration of the cytokine profile and virus-specific immune responses...

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..This is the first report demonstrating that TMEV can induce autoreactive cytotoxic cells that induce central nervous system pathology...

..Interestingly, the ratio of B cells to T cells in cellular infiltrates correlated with clinical score. This suggests that the balance between B and T cells contributes to expression of clinical signs...

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..The difference in inflammation among TMEVs could be due to TGF-beta1 expression that was seen only in GDVII virus infection and negatively correlated with CD3+ T cell infiltration...

..In this review, we compare and contrast the roles of IP-10 between the three animal models for MS, and discuss the relevance to MS patients with different clinical courses...

..The presence of the cell death marker (activated caspase 3) with COX-2 in oligodendrocytes is direct evidence linking COX-2 with cell death of oligodendrocytes in these demyelinating diseases...

..This model will be useful in determining whether transitional forms between CNS (organ)-specific and systemic autoimmune diseases exist, and whether progressive multiple sclerosis has features of a systemic autoimmune disease...

..UV irradiation induced higher anti-MOG antibody responses. In SP-EAE, lymphoproliferative responses and interferon-gamma production were decreased without alteration of interleukin-4...

..We suggest that induction of lymphoid apoptosis alters the balance of Th1 versus Th2 immune responses and increases MOG antibody production, leading to exacerbation of demyelination and subsequent disease progression...

..Autoantibody responses against GFAP are unlikely to play a pathogenic role in autism or Tourette Syndrome...

..To examine the role of innate immunity in a novel viral infection-induced seizure model...

..This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model)...

..We demonstrate the establishment and characterization of a novel virus infection-induced seizure model in C57BL/6 mice...

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..Depletion during the induction phase of the disease resulted in an increase in the incidence of P-EAE and in the clinical score. Overall, B-1 cells were found to modulate EAE pathogenesis...

..These studies indicate that C3 participates in the induction of acute seizures during viral encephalitis...

..In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model)...

..In this study, we demonstrated that TMEV RNA isolated from the spinal cords of chronically infected mice is infectious and that there is at least 30-fold more infectious RNA than infectious virus in the spinal cords of these mice...

..We hypothesized that, in DA virus infection, CD8+ CTLs specific for viral capsid protein could recognize self protein on oligodendrocytes by molecular mimicry, leading to demyelination...

..No differences were found in lymphoproliferative responses to PLP(139-151) among treatment groups. Data suggest that blocking cell-ECM interactions can be an alternative therapy for MS...

..Autoantibody responses against MBP are unlikely to play a pathogenic role in autism...

..Once this priming has occurred, an immunologic challenge could result in disease through bystander activation by cytokines...

..Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism...

..Our results demonstrate that an autoimmune response against myelin could induce pathologic changes in the kidney and may help explain renal changes reported in patients with progressive MS...

..Although A strain mice have been reported to have an insertion in BAFF-R, the receptor for BAFF (B cell activation factor from the tumor necrosis factor family), which could explain our results, A.SW mice have no mutations in BAFF-R...

..These results suggest that the increased inflammatory cell infiltration in TLR2(-/-) C3H mice is the result of localized overproduction of T cell attracting chemokines...

..Conversely, rapid RNA release and resistance to neutralization could favor virus persistence in DA virus infection...

..Importantly, this model will also be useful to investigate novel therapies for the treatment and prevention of epilepsy...

..In virus binding assays to intestine sections, all four TMEVs bound goblet cells and the mucus of the epithelium that was SA dependent. Therefore, differences in SA composition on different cell types can affect tropism and infection...

..Thus, in H101 mutant infections, it appears that elevated levels of cytokines, rather than neuronal cell death, play the dominant role in seizure induction...

..Therefore, both resident CNS cells and infiltrating cells are necessary for seizure development...

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..This suggests that the TMEV receptor on BHK-21 cells could play an important role in cell growth and morphology under physiologic conditions. BHKR- cells should facilitate the search for TMEV receptors...

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..We suggest that the specific removal of such pathogenic epitopes from vaccines might increase their prophylactic potential, while minimizing the risk of side-effects from vaccine use...

..Therefore, new and novel approaches to this disease are warranted. ..

..These new models could help explain the transition from RR disease to progressive disease often observed in MS patients. ..

..The studies not only are important to viral pathogenesis but also the pathogenesis of autoimmune disease. ..

..Our model could provide an explanation why no single microbe has been identified as the MS agent but is likely to be a combination of infectious events. ..

..The third aim is to determine the cellular receptors on CNS and non-CNS cell-types which may be involved in viral tropism and disease. ..

..Therefore, new and novel approaches to this disease are warranted. ..