mortality/aging
• in Con A-treated mice
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immune system
• in vitro, mutant splenocytes show a slight increase in proliferation in response to stimulation with increasing concentrations of anti-CD3 or ConA
• purified mutant splenocytes show a relative increase in the number of cells in the S and G2+M phases of the cell cycle upon stimulation with anti-CD3 plus anti-CD28
• mutant splenocytes show normal dose-response kinetics in response to stimulation with anti-CD3 plus IL-12, but exhibit a higher proliferation rate than wild-type splenocytes at all but the highest dose of IL-12 upon co-stimulation with anti-CD28
|
• homozygotes display only an initial impairment of IFN-gamma production and induction of Th1 responses during the early stages of infection with an intracellular pathogen
(J:89509)
• in a model of experimental autoimmune uveoretinitis, mice exhibit lower Th1 response compared with wild-type mice
(J:116610)
|
• in the early phase of experimental autoimmune uveoretinitis
|
• in Con A-treated mice
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• in Con A-treated mice
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• in Con A-treated mice
|
• in Con A-treated mice
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• in Con A-treated mice
|
• in Con A-treated mice
|
• in vitro, isolated mutant T cells produce decreased IFN-gamma levels upon primary stimulation with IL-12 plus ConA or anti-CD3
(J:89509)
• however, surprisingly, fully differentiated mutant Th1 cells subjected to a secondary stimulation with ConA produce wild-type levels of IFN-gamma
(J:89509)
• in stimulated CD4+ T cells
(J:116610)
|
• in Con A-stimulated liver mononuclear cells
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• in Con A-stimulated liver mononuclear cells
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• in the early phase, with lower Th1 response
• sub-retinal transplants fail to transfer experimental autoimmune uveoretinitis
|
• following infection with Myobacterium bovis bacillus Calmette-Guerin (BCG), homozygotes exhibit 8 times more liver granulomas than control littermates at 2 weeks post-infection
• although mutant granulomas are abnormally large and poorly differentiated, no differences in liver CFU number or liver damage are observed relative to similarly-infected wild-type mice
• although mutant splenocytes produce less IFN-gamma in response to anti-CD3 plus IL-12 than wild-type cells at day 2 post-infection, IFN-gamma production is restored to normal levels at at day 7, and serum IFN-gamma levels are comparable to wild-type levels at 2 weeks post-infection
|
• homozygotes exhibit increased susceptibility to Leishmania major infection, showing increased footpad swelling, more severe footpad ulcerations, and increased parasite burdern relative to control littermates
• infected homozygotes exhibit an abnormal initial Th1 response, as shown by impaired IFN-gamma production by popliteal lymph node CD4+ lymphocytes during the early phases of Leishmania major infection (at day 5 and 2 weeks post-infection), but not during the later phases (at 4 and 6 weeks post-infection) when both IFN-gamma expression and production levels are restored to wild-type levels
• in contrast, IL-4 expression is normal at day 5 but elevated at 2 weeks post-infection or later, concomittant with higher serum levels of IgG1 and IgE at 9 weeks post-infection, indicating a deviation toward a Th2 cytokine profile
|
liver/biliary system
• in Con A-treated mice
|
homeostasis/metabolism
• in the early phase of experimental autoimmune uveoretinitis
|
• in Con A-treated mice
|
• in Con A-treated mice
|
• in Con A-treated mice
|
• in Con A-treated mice
|
• in Con A-treated mice
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• in Con A-treated mice
|
• at a low dose of Con A
• however, treatment with anti-IFN-gamma or anti-IL4 antibodies or depletion of NK cells lowers ALT levels
|
• in Con A-treated mice
|
• mice exhibit increased sensitivity to Con A-induced liver injury with increased mortality and increased cytokine serum levels compared with wild-type mice
• mice treated with a low dose of Con A exhibit increased alanine transaminase serum levels and massive liver necrosis compared with similarly treated wild-type mice
|
hematopoietic system
N |
• homozygotes display normal hematopoietic and lymphoid development relative to wild-type and heterozygous control mice
|
• in vitro, mutant splenocytes show a slight increase in proliferation in response to stimulation with increasing concentrations of anti-CD3 or ConA
• purified mutant splenocytes show a relative increase in the number of cells in the S and G2+M phases of the cell cycle upon stimulation with anti-CD3 plus anti-CD28
• mutant splenocytes show normal dose-response kinetics in response to stimulation with anti-CD3 plus IL-12, but exhibit a higher proliferation rate than wild-type splenocytes at all but the highest dose of IL-12 upon co-stimulation with anti-CD28
|
• homozygotes display only an initial impairment of IFN-gamma production and induction of Th1 responses during the early stages of infection with an intracellular pathogen
(J:89509)
• in a model of experimental autoimmune uveoretinitis, mice exhibit lower Th1 response compared with wild-type mice
(J:116610)
|
cellular
• in vitro, mutant splenocytes show a slight increase in proliferation in response to stimulation with increasing concentrations of anti-CD3 or ConA
• purified mutant splenocytes show a relative increase in the number of cells in the S and G2+M phases of the cell cycle upon stimulation with anti-CD3 plus anti-CD28
• mutant splenocytes show normal dose-response kinetics in response to stimulation with anti-CD3 plus IL-12, but exhibit a higher proliferation rate than wild-type splenocytes at all but the highest dose of IL-12 upon co-stimulation with anti-CD28
|