Analysis Tools
immune system
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• homozygotes exhibit normal numbers of B cells, neutrophils, NK cells, and monocyte/macrophages in lymphoid organs relative to wild-type controls
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• homozygotes display a slight but statistically significant increase in the % of total CD3+ T cells in thymus and peripheral blood relative to wild-type controls
• however, no significant differences in thymus size or thymocyte number are observed
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• homozygotes show a ~2-fold increase in CD4+ T cell number in peripheral blood relative to wild-type controls
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• homozygotes show a ~2-fold increase in CD8+ T cell number in peripheral blood relative to wild-type controls
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• when challenged with protein antigen, mutant T cells hyperproliferate and display a profound polarization towards a Th2 response
• in contrast, Th1-associated responses remain normal
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• in vitro, purified CD4+ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells
• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells
• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a significant increase in TNP-specific IgE titers relative to wild-type controls
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgG2a titers relative to wild-type controls
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgM titers relative to wild-type controls
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• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response
• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation
• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4+ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher Th2 cytokine levels (e.g. IL-4) than wild-type cells
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• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes produce significantly higher IFN-gamma levels than wild-type cells
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• in vitro, purified CD4+ T cells from mutant mice produce significantly higher IL-2 levels than wild-type cells in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28
• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes produce significantly higher IL-2 levels than wild-type cells
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• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response
• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4+ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher IL-4 levels than wild-type cells
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hematopoietic system
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• in vitro, purified CD4+ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells
• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells
• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis
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• homozygotes display a slight but statistically significant increase in the % of total CD3+ T cells in thymus and peripheral blood relative to wild-type controls
• however, no significant differences in thymus size or thymocyte number are observed
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• homozygotes show a ~2-fold increase in CD4+ T cell number in peripheral blood relative to wild-type controls
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• homozygotes show a ~2-fold increase in CD8+ T cell number in peripheral blood relative to wild-type controls
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a significant increase in TNP-specific IgE titers relative to wild-type controls
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgG2a titers relative to wild-type controls
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• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgM titers relative to wild-type controls
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• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response
• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation
• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4+ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher Th2 cytokine levels (e.g. IL-4) than wild-type cells
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homeostasis/metabolism
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• following stimulation with anti-CD3 plus anti-CD-28 for 48 hrs, purified mutant splenic CD4+ T cells show a significant reduction in JNK activity relative to wild-type cells
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cellular
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• in vitro, purified CD4+ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells
• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells
• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis
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