immune system
N |
• homozygotes exhibit normal lymphoid tissue morphology with normal lymphoid cell populations in bone marrow, lymph node and spleen relative to wild-type controls
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• in culture, total splenocytes from homozygous mutant mice display significantly decreased CTL activity against allogeneic P815 mastocytoma (H-2d) target cells relative to wild-type splenocytes
• however, purified mutant CD8+ effector cells exhibit normal CTL activity against P815 cells on a per cell basis relative to wild-type CD8+ cells
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• upon activation with anti-CD3 and anti-CD28, mutant CD8+ T cells exhibit severely reduced cell-surface expression levels of IL-2 receptor (CD25) relative to wild-type cells, suggesting impaired IL-2 signaling
• addition of exogenous IL-12 increases CD25 cell-surface levels on mutant CD8+ T cells to a lesser extent than in wild-type CD8+ T cells (68.9 +/- 10.4% vs 90.6 +/- 1.6%, respectively)
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• homozygotes display significantly reduced CD8+ (but not CD4+) T cell proliferation in response to TCR or TCR plus CD28-mediated stimulation, by determined by [3H]thymidine incorporation
• in a mixed lymphocyte reaction (MLR) assay, purified mutant CD8+ T cells display significantly reduced proliferation in response to allogeneic P815 mastocytoma (H-2d) stimulator cells
• impaired CD8+ T cell proliferation is at least partly due to defects in cell division progression, in the absence of increased CD8+ T cell apoptosis
• following activation by anti-CD3 and anti-CD28, mutant CD8+ T cells show a significantly reduced proliferative response to exogenous rmIL-2 relative to wild-type cells
• addition of exogenous IL-12 increases cell-surface expression of CD25 on mutant CD8+ T cells but fails to ameliorate the proliferative defect
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hematopoietic system
• in culture, total splenocytes from homozygous mutant mice display significantly decreased CTL activity against allogeneic P815 mastocytoma (H-2d) target cells relative to wild-type splenocytes
• however, purified mutant CD8+ effector cells exhibit normal CTL activity against P815 cells on a per cell basis relative to wild-type CD8+ cells
|
• upon activation with anti-CD3 and anti-CD28, mutant CD8+ T cells exhibit severely reduced cell-surface expression levels of IL-2 receptor (CD25) relative to wild-type cells, suggesting impaired IL-2 signaling
• addition of exogenous IL-12 increases CD25 cell-surface levels on mutant CD8+ T cells to a lesser extent than in wild-type CD8+ T cells (68.9 +/- 10.4% vs 90.6 +/- 1.6%, respectively)
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• homozygotes display significantly reduced CD8+ (but not CD4+) T cell proliferation in response to TCR or TCR plus CD28-mediated stimulation, by determined by [3H]thymidine incorporation
• in a mixed lymphocyte reaction (MLR) assay, purified mutant CD8+ T cells display significantly reduced proliferation in response to allogeneic P815 mastocytoma (H-2d) stimulator cells
• impaired CD8+ T cell proliferation is at least partly due to defects in cell division progression, in the absence of increased CD8+ T cell apoptosis
• following activation by anti-CD3 and anti-CD28, mutant CD8+ T cells show a significantly reduced proliferative response to exogenous rmIL-2 relative to wild-type cells
• addition of exogenous IL-12 increases cell-surface expression of CD25 on mutant CD8+ T cells but fails to ameliorate the proliferative defect
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cellular
• homozygotes display significantly reduced CD8+ (but not CD4+) T cell proliferation in response to TCR or TCR plus CD28-mediated stimulation, by determined by [3H]thymidine incorporation
• in a mixed lymphocyte reaction (MLR) assay, purified mutant CD8+ T cells display significantly reduced proliferation in response to allogeneic P815 mastocytoma (H-2d) stimulator cells
• impaired CD8+ T cell proliferation is at least partly due to defects in cell division progression, in the absence of increased CD8+ T cell apoptosis
• following activation by anti-CD3 and anti-CD28, mutant CD8+ T cells show a significantly reduced proliferative response to exogenous rmIL-2 relative to wild-type cells
• addition of exogenous IL-12 increases cell-surface expression of CD25 on mutant CD8+ T cells but fails to ameliorate the proliferative defect
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