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Allele Symbol Allele Name Allele ID |
Tg(DO11.10)10Dlo transgene insertion 10, Dennis Y Loh MGI:2664398 |
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| Summary |
28 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• positive selection of CD4+ cells is severely impaired compared to in DO11.10 TCR control mice
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• positive selection of CD4+ cells is severely impaired compared to in DO11.10 TCR control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 10-fold reduction
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• partial impairment in generation of double positive cells
• partial arrest at the double negative 3 (DN3) to double negative 4 (DN4) transition
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• 10-fold reduction
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• 10-fold reduction
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• partial impairment in generation of double positive cells
• partial arrest at the double negative 3 (DN3) to double negative 4 (DN4) transition
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• 10-fold reduction
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severe reduction in single positive (SP) CD4 cells and no enrichment of SP CD8 cells
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• severe reduction in single positive (SP) CD4 cells and no enrichment of SP CD8 cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the mean survival time is 4 months, which is significantly shorter than the average life expectancy of BALB/C mic
• however, the mean survival time is much longer than Il2 null mice on a BALB/c background that do not carry the TCR transgene
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• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen
• CD 4 T cells from these transfer experiments also express high levels of activation markers
• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter
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• when transferred into athymic mice, there are 10-100 fold higher numbers of activated T cells three weeks after antigen
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• the abnormal proliferation of CD4 T cells upon transfer into athymic mice is reduced by the addition of wild-type CD4-postive CD25-positive T cells
• this suggests there is a defect in the regulatory T cell population in these mice
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• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen
• CD 4 T cells from these transfer experiments also express high levels of activation markers
• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter
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• when transferred into athymic mice, there are 10-100 fold higher numbers of activated T cells three weeks after antigen
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• the abnormal proliferation of CD4 T cells upon transfer into athymic mice is reduced by the addition of wild-type CD4-postive CD25-positive T cells
• this suggests there is a defect in the regulatory T cell population in these mice
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• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen
• CD 4 T cells from these transfer experiments also express high levels of activation markers
• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• IFN-alpha stimulation does not promote Th1 cell development similar to Stat2 wild-type mice and unlike in humans
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• enhanced positive selection, resulting in an increase in the number of cells that mature to the single positive stage relative to wild-type
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• enhanced positive selection, resulting in an increase in the number of cells that mature to the single positive stage relative to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when transgenic mutant mice are injected with OVA, there is little induction of CD69+ on CD4+ T cells; CD69+ expression is significantly induced on CD 4+ cells of nontransgenic Tpte2-deficient controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• induced by Fas
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• induced by Fas
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• induced by Fas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• naive T cells are able to initiate a response to antigen but show decreased sensitivity to lower antigen concentrations and are unable to maintain their proliferative response
• naive CD4+ antigen-specific T cell responses to mitogen (Con A) activation are reduced in splenocytes
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• thymocyte proliferative responses to OVA antigen are reduced
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• 10- to 20-fold decrease in T cell IL-2 production when stimulated with OVA antigen
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• naive T cells are able to initiate a response to antigen but show decreased sensitivity to lower antigen concentrations and are unable to maintain their proliferative response
• naive CD4+ antigen-specific T cell responses to mitogen (Con A) activation are reduced in splenocytes
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• thymocyte proliferative responses to OVA antigen are reduced
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• thymocyte proliferative responses to OVA antigen are reduced
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• naive T cells are able to initiate a response to antigen but show decreased sensitivity to lower antigen concentrations and are unable to maintain their proliferative response
• naive CD4+ antigen-specific T cell responses to mitogen (Con A) activation are reduced in splenocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• single positive cell number in thymus
• transgene positive CD4 cells in spleen, lymph node and blood
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• single positive cell number in thymus
• transgene positive CD4 cells in spleen, lymph node and blood
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Th2 T cells from these mice fail to induce airway hyperresponsive when transferred to immunodeficient hosts
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• lymphocytes fail to produce IL-13
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• Th2 T cells from these mice fail to induce airway hyperresponsive when transferred to immunodeficient hosts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• significantly reduced ability of T regulatory cells to enter mesenteric and peripheral lymph nodes
• more moderately reduced ability of T regulatory cells to enter Peyer's patches and the gut
• greater ability to migrate into the liver
• failure of T regulatory cells to localize to T cell zones of lymph nodes
• reduced movement of T regulatory cells away from peripheral sites of inflammation
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• significantly reduced ability of T regulatory cells to enter mesenteric and peripheral lymph nodes
• more moderately reduced ability of T regulatory cells to enter Peyer's patches and the gut
• greater ability to migrate into the liver
• failure of T regulatory cells to localize to T cell zones of lymph nodes
• reduced movement of T regulatory cells away from peripheral sites of inflammation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• size reduced 3 fold
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• increased apoptosis of double positive cells
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• size reduced 3 fold
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• increased apoptosis of double positive cells
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• size reduced 3 fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• a marked reduction in the proportion and absolute numbers of CD4 SP thymocytes, and lower percentages and lower absolute numbers of CD4+ T cells expressing the transgene in the spleens and lymph nodes
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• a marked reduction in the proportion and absolute numbers of CD4 SP thymocytes, and lower percentages and lower absolute numbers of CD4+ T cells expressing the transgene in the spleens and lymph nodes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mild splenomegaly observed in 6-8 week-old mice
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• 3 to 4 days after priming with ovalbumin peptide and antigen-presenting cells, T cells produce Il-4, whereas Ctla4-sufficient, Tg(DO11.10)10Dlo cells do not
• T cells produce Th2 cytokines (Il-4, Il-5, and Il-10) upon restimulation with antigen and APCs, whereas Tg(DO11.10)10Dlo cells produce the Th1 cytokine interferon gamma; Th2 bias is seen over a range of peptide concentration during primary stimulation
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• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells
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• mild splenomegaly observed in 6-8 week-old mice
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• 3 to 4 days after priming with ovalbumin peptide and antigen-presenting cells, T cells produce Il-4, whereas Ctla4-sufficient, Tg(DO11.10)10Dlo cells do not
• T cells produce Th2 cytokines (Il-4, Il-5, and Il-10) upon restimulation with antigen and APCs, whereas Tg(DO11.10)10Dlo cells produce the Th1 cytokine interferon gamma; Th2 bias is seen over a range of peptide concentration during primary stimulation
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• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells
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• mild lymphadenopathy observed in 6-8 week-old mice
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• mild splenomegaly observed in 6-8 week-old mice
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• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• isolated T cells primed under Th2 conditions for 5 days, restimulated for 5 more days, then restimulated in absence of exogenous cytokine fail to produce Il4, although cell expansion is similar to wild-type; PMA/ionomycin restimulation of Th2-primed cells restores Il4 secretion
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• isolated T cells primed under Th2 conditions for 5 days, restimulated for 5 more days, then restimulated in absence of exogenous cytokine fail to produce Il4, although cell expansion is similar to wild-type; PMA/ionomycin restimulation of Th2-primed cells restores Il4 secretion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following anti-CD3 antibody stimulation, differentiation into Th17 cells is increased compared to in wild-type mice
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• following ovalbumin stimulation or infection with Listeriosis monocytogenes, Il-22 plasma levels are increased compared to in wild-type mice
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• following ovalbumin stimulation or infection with Listeriosis monocytogenes
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• following anti-CD3 antibody stimulation
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• mice are resistant to infection with Listeriosis monocytogenes with a 45-fold less bacteria load in the spleen and a 150-fold less bacterial load in the liver after re-challenge compared to in similarly treated wild-type mice
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• following ovalbumin stimulation or infection with Listeriosis monocytogenes, Il-22 plasma levels are increased compared to in wild-type mice
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• following ovalbumin stimulation or infection with Listeriosis monocytogenes
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• following anti-CD3 antibody stimulation, differentiation into Th17 cells is increased compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the development of IL-4+IFNG- and IFNG+IL-4- T cells after immunization are increased but not if wild-type splenocytes are transferred into mutant mice
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• germinal center formation is increased in mutants but not if wild-type splenocytes are transferred into mutant mice
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• following immunization with a cross-linked OVA-HA antigen IgE levels are elevated by 2 orders of magnitude compared to mutant mice wild-type for Rag1; however serum Ig half-lives are normal
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• following immunization with a cross-linked OVA-HA antigen IgG titers are increased compared to mutant mice wild-type for Rag1, with IgG1 titers increased about 20-fold
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• the development of IL-4+IFNG- and IFNG+IL-4- T cells after immunization are increased but not if wild-type splenocytes are transferred into mutant mice
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• germinal center formation is increased in mutants but not if wild-type splenocytes are transferred into mutant mice
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• following immunization with a cross-linked OVA-HA antigen IgE levels are elevated by 2 orders of magnitude compared to mutant mice wild-type for Rag1; however serum Ig half-lives are normal
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• following immunization with a cross-linked OVA-HA antigen IgG titers are increased compared to mutant mice wild-type for Rag1, with IgG1 titers increased about 20-fold
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hyper IgE recurrent infection syndrome 1 | DOID:3261 |
OMIM:147060 |
J:100072 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show no signs of T cell activation, lymphadenopathy, or splenomegaly over 32 weeks; T cells are naive, with no expression of activation markers
• primary response to antigen stimulation in vitro is similar to Rag1-null, Tg(DO11.10)10Dlo T cells
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• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice
• transferred T cells are resistant to tolerance induction in vivo in hosts after a tolerizing dose of ovalbumin peptide; in vivo expansion of T cells 4 and 7 days after treatment is 2.2- and 1.4-fold greater than Rag2-null, transgenic mice
• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice
• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1
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• during secondary response, on days 2 and 3, T cells show increased production of interferon gamma and Il-4 than transgenic, Rag2-null mice
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• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice
• transferred T cells are resistant to tolerance induction in vivo in hosts after a tolerizing dose of ovalbumin peptide; in vivo expansion of T cells 4 and 7 days after treatment is 2.2- and 1.4-fold greater than Rag2-null, transgenic mice
• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice
• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• transgenic T cell development is arrested after positive selection but before CD4+T cell lineage commitment
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• mice exhibit severe lymphopenia with only a minor population of CD8+ T cells found in the spleen
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• transgenic T cell development is arrested after positive selection but before CD4+T cell lineage commitment
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• mice exhibit severe lymphopenia with only a minor population of CD8+ T cells found in the spleen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• T cells exhibit similar levels of activation induced cell death as Rag2-, Ctla4-deficient, Tg (DO11.10)10Dlo T cells
• cells undergo tolerance induction in vivo in response to an immunizing or tolerizing stimulus
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fully polarized TH1 cells show a 2-fold increase in proliferation in response to OVA peptide presented by either CD8+ or CD8-CD11c+ DCs
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• fully polarized TH1 cells show a 2-fold increase in proliferation in response to OVA peptide presented by either CD8+ or CD8-CD11c+ DCs
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• fully polarized TH1 cells show a 2-fold increase in proliferation in response to OVA peptide presented by either CD8+ or CD8-CD11c+ DCs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• impaired positive selection
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• marked reduction in CD4+ single positive t cells after ovalbumin administration relative to controls
• both CD4+ and CD8+ single positive splenocytes reduced after ovalbumin administration
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• enhanced generation of TH2 cells
• TH1 differentiation unaffected
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• impaired positive selection
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• marked reduction in CD4+ single positive t cells after ovalbumin administration relative to controls
• both CD4+ and CD8+ single positive splenocytes reduced after ovalbumin administration
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• enhanced generation of TH2 cells
• TH1 differentiation unaffected
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• CD4+ T cells produce less IL-4 following treatment with OVA peptide-pulsed antigen presenting cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased T cell proliferation when stimulated with ovalbumin peptide
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• cultured T cells under conditions that promote either Th1 or Th2 differentiation fail to produce appreciable amounts of IFNG or IL4
• addition of supplemental IL2 allows for normal Th1 and Th2 differentiation
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• at 24, 48, and 72 h after stimulation compared to controls
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• decreased T cell proliferation when stimulated with ovalbumin peptide
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• cultured T cells under conditions that promote either Th1 or Th2 differentiation fail to produce appreciable amounts of IFNG or IL4
• addition of supplemental IL2 allows for normal Th1 and Th2 differentiation
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• decreased T cell proliferation when stimulated with ovalbumin peptide
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells
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• number of CD4+CD8- mature thymocytes decreases to ~20% that in control Tg(DO11.10)10Dlo mice
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• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells
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• number of CD4+CD8- mature thymocytes decreases to ~20% that in control Tg(DO11.10)10Dlo mice
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• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• CD4+ T cells produce less IL-4 following treatment with OVA peptide-pulsed antigen presenting cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 20 hours after administration of OVA323-339 peptide, apoptosis, DNA degradation, chromatin condensation, and cell shrinkage occur in the majority of cortical thymocytes
• apoptosis occurs throughout the thymus including the subcapsular and deep cortical areas
• 3 days after administration of peptide the cortical thymus is acellular; however, normal cellularity exists in the medulla
• peptide administration does not effect small number of thymocytes that express only the beta chain transgene Vb8
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• CD4+CD8+TCR
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• CD4+ CD8- TCR
thymocytes are reduced in absolute numbers after administration of OVA 323-339 peptide
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• 20 hours after administration of OVA323-339 peptide, apoptosis, DNA degradation, chromatin condensation, and cell shrinkage occur in the majority of cortical thymocytes
• apoptosis occurs throughout the thymus including the subcapsular and deep cortical areas
• 3 days after administration of peptide the cortical thymus is acellular; however, normal cellularity exists in the medulla
• peptide administration does not effect small number of thymocytes that express only the beta chain transgene Vb8
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• CD4+CD8+TCR
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• CD4+ CD8- TCR
thymocytes are reduced in absolute numbers after administration of OVA 323-339 peptide
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• 20 hours after administration of OVA323-339 peptide, apoptosis, DNA degradation, chromatin condensation, and cell shrinkage occur in the majority of cortical thymocytes
• apoptosis occurs throughout the thymus including the subcapsular and deep cortical areas
• 3 days after administration of peptide the cortical thymus is acellular; however, normal cellularity exists in the medulla
• peptide administration does not effect small number of thymocytes that express only the beta chain transgene Vb8
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 07/05/2024 MGI 6.24 |
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