Analysis Tools
immune system
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• in culture, mutant macrophages express significantly more Mac-1 after IFN-gamma and LPS stimulation relative to wild-type macrophages
• in response to IFN-gamma and LPS stimulation, mutant macrophages display a greater down-regulation of VCAM-1 than wild-type macrophages
• unlike in wild-type cultures where TNF levels reach a peak at 10 hrs of stimulation and then slowly decline over 24 hrs, mutant macrophages continue to express elevated levels of TNF without reaching a plateau
• other macrophage-specific cytokines, such as IL-12 and IL-1beta, remain unaffected
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• during the chronic phase of EAE (day 64 post-infection), homozygotes show a significant higher number of Mac-1-positive activated residual microglia throughout the CNS parenchyma than wild-type controls
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• during both the acute and chronic phase of EAE, homozygotes show a significantly higher IFN-gamma production than wild-type controls
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• during the chronic phase of EAE, homozygotes exhibit a significantly higher IL-4 production in the CNS relative to wild-type controls
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• during the chronic phase of EAE, homozygotes exhibit a significantly higher TNF production in the CNS relative to wild-type controls
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• in response to immunization with myelin basic protein 89-101 (MBP89-101) peptide, affected homozygotes develop a more severe and chronic EAE with a higher incidence than wild-type controls
• unlike in wild-type controls, where most mice recover after the initial paralysis and only 40% show clinical symptoms by the end of the experiment, most affected homozygotes continue to show an increase in disease severity, develop chronic disease or suffer relapses such that 90% still exhibit EAE by 64 days post-infection
• during the chronic phase, EAE-immunized homozygotes develop significantly more relapses, a higher mean maximal clinical score, and a higher accumulative score than wild-type controls
• no differences in autoreactive T cell priming are observed, as mutant T cells retain their capacity to proliferate in vitro and produce IFN-gamma and IL-4 in response to recall Ag
• when EAE is induced by passive transfer, mutant recipient mice develop significantly more severe EAE with a higher incidence than wild-type controls regardless of the origin of encephalitogenic T cells
• no differences in MBP-specific total IgG or IgG2a or n MOG-specific IgG are observed between homozygous mutant and wild-type control mice
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• during the acute phase of EAE (day 12 post-infection), homozygotes display significantly more infiltrating T cells, activated macrophages, and MHC II-expressing cells in the CNS than wild-type controls
• during the chronic phase of EAE (day 64 post-infection), homozygotes display a generalized amplified inflammatory CNS response with increased levels of TNF, IFN-gamma, and IL-4, higher numbers of activated microglia but no differences in infiltrating cell numbers relative to wild-type controls
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nervous system
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• during the chronic phase of EAE (day 64 post-infection), homozygotes show a significant higher number of Mac-1-positive activated residual microglia throughout the CNS parenchyma than wild-type controls
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• during the acute phase of EAE (day 12 post-infection), homozygotes display significantly more infiltrating T cells, activated macrophages, and MHC II-expressing cells in the CNS than wild-type controls
• during the chronic phase of EAE (day 64 post-infection), homozygotes display a generalized amplified inflammatory CNS response with increased levels of TNF, IFN-gamma, and IL-4, higher numbers of activated microglia but no differences in infiltrating cell numbers relative to wild-type controls
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demyelination
(
J:83021
)
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• at 64 days after induction of active EAE, homozygotes display a significantly higher degree of demyelination than wild-type controls
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hematopoietic system
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• in culture, mutant macrophages express significantly more Mac-1 after IFN-gamma and LPS stimulation relative to wild-type macrophages
• in response to IFN-gamma and LPS stimulation, mutant macrophages display a greater down-regulation of VCAM-1 than wild-type macrophages
• unlike in wild-type cultures where TNF levels reach a peak at 10 hrs of stimulation and then slowly decline over 24 hrs, mutant macrophages continue to express elevated levels of TNF without reaching a plateau
• other macrophage-specific cytokines, such as IL-12 and IL-1beta, remain unaffected
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• during the chronic phase of EAE (day 64 post-infection), homozygotes show a significant higher number of Mac-1-positive activated residual microglia throughout the CNS parenchyma than wild-type controls
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