immune system
• CD4 T cell development is blocked at the double positive stage 3 step where high surface expression of TCR beta is needed to develop precursors into mature CD4+ T cells
• analysis of various developmental markers (Bim, Rag1, Gata3, Zbtb7b) places developmental arrest of CD4 T cells after positive selection of the TCR but before CD4 T cell lineage commitment
• this defect is intrinsic to the T cell precursors as revealed by mixed bone marrow chimera experiments in irradiated wild-type hosts
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• CD4+ and CD4+CD8lo thymocytes are virtually absent in the thymus
• there are 24- and 16-fold reductions in the frequency and absolute number of splenic CD4+ T cells compared to wild-type controls
• splenic CD4+ T cells are also CD44+ indicating a large expansion of a few CD4 T cells that manage to develop in the thymus
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• NKT cells are severely reduced both in the thymus and spleen
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• the frequency of Foxp3+ T cells in the thymus is reduced more than 10-fold
• few Foxp3+ T cells are found in the spleen with the many of these cells not expression CD4 or CD25
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• 42% of CD8+ T cells are also CD44+ indicating an expansion of the CD8+ T cell population that leaves the thymus
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• CD8+ T cells have a some reduction in cytoxic activity compared to controls
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hematopoietic system
• CD4 T cell development is blocked at the double positive stage 3 step where high surface expression of TCR beta is needed to develop precursors into mature CD4+ T cells
• analysis of various developmental markers (Bim, Rag1, Gata3, Zbtb7b) places developmental arrest of CD4 T cells after positive selection of the TCR but before CD4 T cell lineage commitment
• this defect is intrinsic to the T cell precursors as revealed by mixed bone marrow chimera experiments in irradiated wild-type hosts
|
• CD4+ and CD4+CD8lo thymocytes are virtually absent in the thymus
• there are 24- and 16-fold reductions in the frequency and absolute number of splenic CD4+ T cells compared to wild-type controls
• splenic CD4+ T cells are also CD44+ indicating a large expansion of a few CD4 T cells that manage to develop in the thymus
|
• NKT cells are severely reduced both in the thymus and spleen
|
• the frequency of Foxp3+ T cells in the thymus is reduced more than 10-fold
• few Foxp3+ T cells are found in the spleen with the many of these cells not expression CD4 or CD25
|
• 42% of CD8+ T cells are also CD44+ indicating an expansion of the CD8+ T cell population that leaves the thymus
|
• CD8+ T cells have a some reduction in cytoxic activity compared to controls
|