mortality/aging
• with injection of diptheria toxin (DT) in newborns at 12 hours after birth and then every other day thereafter, 40% of mutants become moribund by 24 days
• remaining treated female mutants at weaning are moribund within 27 days of age
• adult female mutants treated with DT become moribund beginning at 10 days post-injection and all are dead after 3 weeks of treatment (regulatory T cell ablation)
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growth/size/body
weight loss
(
J:117743
)
• observed in newborn and adult mutants treated with DT
|
• observed in 3-week old mutants treated daily with DT
• also seen in 3-month old adult mutants treated with DT
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immune system
• observed in 3-week old mutants treated daily with DT
• also seen in 3-month old adult mutants treated with DT
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• numbers are elevated after Treg ablation
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• injection of 50 ug/kg DT at 0 and 24 hours almost completely eliminates all regulatory T cells (Treg) in 2 days
• thymic T cells rebound to 47% of pre-treatment numbers after 4 days and recovers fully by 10 days; peripheral (lymph nodes and spleen) (Treg) numbers recover to 8 and 6% by 2 days and fully recover to pre-treatment levels between 10 and 15 days after injection
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• Foxp3-null CD4+ T cells from DT-treated female mutants have higher T cell activation marker levels than cells from treated controls, as well as proliferation markers
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• in mutants after Treg ablation
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• observed in 3-week old mutants treated daily with DT compared to untreated mutant littermates
• also seen in 3-month old adult mutants treated with DT
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• female mutants treated with DT rapidly develop terminal autoimmune disease resulting from (Treg) elimination; adult mice develop disease more rapidly than newborn mutants
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• newborns treated with DT 12 hours after birth exhibit conjunctivitis; adults treated with DT show severe conjunctivitis
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• massive lymphocytic and mononuclear infiltrates in liver sinusoids seen at 3 weeks with DT treatment
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• massive lymphocytic and mononuclear infiltrates in lung interstitium seen at 3 weeks with DT treatment
|
dermatitis
(
J:117743
)
• massive lymphocytic and mononuclear infiltrates in epidermis seen at 3 weeks with DT treatment
|
hematopoietic system
• observed in 3-week old mutants treated daily with DT
• also seen in 3-month old adult mutants treated with DT
|
• numbers are elevated after Treg ablation
|
• injection of 50 ug/kg DT at 0 and 24 hours almost completely eliminates all regulatory T cells (Treg) in 2 days
• thymic T cells rebound to 47% of pre-treatment numbers after 4 days and recovers fully by 10 days; peripheral (lymph nodes and spleen) (Treg) numbers recover to 8 and 6% by 2 days and fully recover to pre-treatment levels between 10 and 15 days after injection
|
• Foxp3-null CD4+ T cells from DT-treated female mutants have higher T cell activation marker levels than cells from treated controls, as well as proliferation markers
|
behavior/neurological
bradykinesia
(
J:117743
)
• moribund newborns and adults treated with DT display lack of mobility
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liver/biliary system
• massive lymphocytic and mononuclear infiltrates in liver sinusoids seen at 3 weeks with DT treatment
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respiratory system
• massive lymphocytic and mononuclear infiltrates in lung interstitium seen at 3 weeks with DT treatment
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vision/eye
• newborns treated with DT 12 hours after birth exhibit conjunctivitis; adults treated with DT show severe conjunctivitis
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integument
dermatitis
(
J:117743
)
• massive lymphocytic and mononuclear infiltrates in epidermis seen at 3 weeks with DT treatment
|