Analysis Tools
immune system
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• homozygotes display normal T and B lymphocyte development, with no differences in thymus or spleen size relative to wild-type controls
• in culture, mutant splenic B cells show normal proliferation to anti-IgM and anti-CD40 stimulation as well as normal activation of NF-kappaB and AP-1 following CD40 ligation
• homozygotes display normal antibody responses to T-dependent antigens (ovalbumin) and type 1 and type 2 T-independent antigens (TNP-LPS and TNP-Ficoll, respectively)
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• in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
• increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
• following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation
• proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)
• however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
• activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
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• homozygotes show a significant increase of total lymphocyte number in inguinal lymph nodes relative to wild-type controls
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• homozygotes exhibit an increased T/B cell ratio in inguinal lymph nodes relative to wild-type controls
• however, the CD4/CD8 ratio remains normal
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hematopoietic system
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• in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
• increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
• following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation
• proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)
• however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
• activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
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• homozygotes show a significant increase of total lymphocyte number in inguinal lymph nodes relative to wild-type controls
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cellular
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• homozygotes display increased sensitivity to TNF-induced skin necrosis relative to wild-type controls
• following subcutaneous injection of a suboptimal TNF dose (1.5 ug/day for 5 days), homozygotes display significantly more skin ulcerations and hemorrhages than wild-type controls, with complete loss of the epidermis and extensive cellular damage in dermis and hypodermis, including vacuolization and disintegration
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• in culture, mutant splenic T cells show higher proliferation to immobilized anti-CD3 mAb than wild-type T cells; however, no differences in annexin V staining, expression of CD25 (IL-2R-alpha) or intracellular IL-2 protein content are observed
• increased T cell proliferation persists following stimulation with submitogenic concentrations of anti-CD3 mAb and increasing concentrations of CD28 mAb or of recombinant IL-2
• following prestimulation with anti-CD3 mAb, activated mutant, but not wild-type, T cells, respond to TNF by proliferation, as determined by [3H]-thymidine incorporation
• proliferation of activated mutant T cells to TNF is abrogated by antagonistic mAb to TNF receptor superfamily, member 1b (TNFR2, p75) but not by antagonistic mAb to TNF receptor superfamily, member 1a (TNFR1, p55)
• however, following injection of staphylococcal enterotoxin B (SEB), homozygotes display normal superantigen-induced clonal expansion and deletion of peripheral Vbeta8-bearing T cells, as determined by changes in lymph node Vbeta8+ and Vbeta6+ subsets, BrdU incorporation of Vbeta8-bearing T cells, and apoptosis of CD4+ and CD8+ populations by annexin V-FITC staining
• activated mutant, but not wild-type, T cells respond to TNF by activation of the NF-kappaB and AP-1 signaling pathways
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