mortality/aging
• diphtheria toxin-treated mice produce a large spike of IFN-gamma and TNF-alpha before developing cachexia and dying unlike similarly treated wild-type mice
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immune system
• irradiated wild-type mice reconstituted with bone marrow from Tg(Itgax-DTR/EGFP)57Lan that have received Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi and wild-type myeloid dendritic cells and have been treated with diphtheria toxin develop insulitis
• however, use of plasmocytoid dendritic cells instead of myeloid dendritic cells fails to restore development of insulitis
• mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells and treated with diphtheria toxin exhibit an acceleration of insulitis
• mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi and wild-type plasmocytoid dendritic cells and treated with diphtheria toxin exhibit delay in the development of insulitis
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• diphtheria toxin-treated mice exhibit ablation of all major dendritic cells from the spleen, pancreas, and lymph nodes unlike similarly treated wild-type mice
• diptheria toxin-treated mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells exhibit a loss of intrapancreatic plasmacytoid dendritic cells
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• diptheria toxin-treated mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells exhibit a loss of intrapancreatic NK T cells
• however, spleen and nondraining secondary lymphoid compartments exhibit normal NK T cell numbers and the addition of plasmocytoid dendritic cells to mice restores pancreatic NK T cell numbers
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• diphtheria toxin-treated mice exhibit macrophage loss that is less than 5% to 8%
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• antigen presenting cells from irradiated wild-type mice reconstituted with bone marrow from Tg(Itgax-DTR/EGFP)57Lan that have received Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells have been treated with diphtheria toxin fail to present either peptide or whole islet cells to naive BDC2.5 T cells over a wide range of antigen concentrations unlike PBS-treated mice
• however, additional treatment with wild-type myeloid dendritic cells restores antigen presentation
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• in diphtheria toxin-treated mice
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• in diphtheria toxin-treated mice
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• irradiated wild-type mice reconstituted with bone marrow from Tg(Itgax-DTR/EGFP)57Lan that have received Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells have been treated with diphtheria toxin do not develop diabetes unlike PBS-treated mice
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endocrine/exocrine glands
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• irradiated wild-type mice reconstituted with bone marrow from Tg(Itgax-DTR/EGFP)57Lan that have received Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells have been treated with diphtheria toxin fail to develop insulitis unlike PBS-treated mice
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• irradiated wild-type mice reconstituted with bone marrow from Tg(Itgax-DTR/EGFP)57Lan that have received Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi and wild-type myeloid dendritic cells and have been treated with diphtheria toxin develop insulitis
• however, use of plasmocytoid dendritic cells instead of myeloid dendritic cells fails to restore development of insulitis
• mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells and treated with diphtheria toxin exhibit an acceleration of insulitis
• mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi and wild-type plasmocytoid dendritic cells and treated with diphtheria toxin exhibit delay in the development of insulitis
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growth/size/body
hematopoietic system
• diphtheria toxin-treated mice exhibit ablation of all major dendritic cells from the spleen, pancreas, and lymph nodes unlike similarly treated wild-type mice
• diptheria toxin-treated mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells exhibit a loss of intrapancreatic plasmacytoid dendritic cells
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• diptheria toxin-treated mice receiving Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi cells exhibit a loss of intrapancreatic NK T cells
• however, spleen and nondraining secondary lymphoid compartments exhibit normal NK T cell numbers and the addition of plasmocytoid dendritic cells to mice restores pancreatic NK T cell numbers
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• diphtheria toxin-treated mice exhibit macrophage loss that is less than 5% to 8%
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