immune system
• 24 hours after exposure to 200 ug of CII tolerogen, T cells show a greatly reduced capacity to proliferate on CII stimulus compared to T cells from mice exposed to 200 ug of OVA; 48 hours after CII exposure, T cells are refractory to stimulation by CII peptide up to 130 uM
• after 72 hours, CII-tolerized cells can be stimulated by CII concentrations that are >2 logs higher than that needed to stimulate OVA-tolerized transgenic T cells
• suppressed proliferative response is observed up to 7 days post-CII treatment
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• when stimulated in vitro with CII (type II collagen) or a CII peptide, naive T cells show a vigorous proliferative response, while non-transgenic T cells do not
• proliferation of CII-tolerized T cells can be restored when cultured with CII and very high Il2 concentrations
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• following CII-tolerization, transgenic T cells from the spleen show increased levels of activation markers CD69 and CD71, compared to OVA-tolerized transgenic mice
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• markers (CD44high and CD62low) for memory T cell phenotypes are increased in CII-tolerized cells
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• after overnight CII stimulation, CII-treated T cells produce equivalent levels of Il2 as OVA-treated T cells, but by 48 hours after tolerization, the Il2 response is reduced
• by 48 hours after tolerance induction, production of Th2 cytokines like Il4 and Il10 are enhanced in T cells from CII-treated mice compared to those from OVA-treated mice
• IFNgamma production is elevated in cultures from CII-treated mice
• without CII peptide stimulation, no cytokines can be detected in cultures
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• when immunized with an emulsion containing CII and CFA, mice develop strong T-cell dependent antibody response to the immunogen and the autoantigen, murine CII
• in arthritis incidence in transgenic mice; 100 % of mice tolerized with OVA develop arthritis by day 24 at an accelerated rate, but only 2 mice tolerized with CII develop disease by 42 days
• when mice are tolerized with 3 consecutive doses of 200 ug OVA or CII, no CII-tolerized mice develop arthritis, whereas all OVA-tolerized mice develop disease by day 13
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• immunized mice develop severe accelerated autoimmune arthritis as early as 11 days after immunization with maximum incidence and severity by 35 days compared to non-transgenic littermates which develop arthritis around day 20 and maximum incidence by day 50 which is similar to that seen in wild-type DBA/1 mice
• however, no spontaneous arthritis has been observed in transgenic mice up to 9 months of age
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• levels of anti-CII antibody levels are higher than in controls littermates at day 19, but at day 34 levels are high in both groups of mice
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hematopoietic system
• 24 hours after exposure to 200 ug of CII tolerogen, T cells show a greatly reduced capacity to proliferate on CII stimulus compared to T cells from mice exposed to 200 ug of OVA; 48 hours after CII exposure, T cells are refractory to stimulation by CII peptide up to 130 uM
• after 72 hours, CII-tolerized cells can be stimulated by CII concentrations that are >2 logs higher than that needed to stimulate OVA-tolerized transgenic T cells
• suppressed proliferative response is observed up to 7 days post-CII treatment
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• when stimulated in vitro with CII (type II collagen) or a CII peptide, naive T cells show a vigorous proliferative response, while non-transgenic T cells do not
• proliferation of CII-tolerized T cells can be restored when cultured with CII and very high Il2 concentrations
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• following CII-tolerization, transgenic T cells from the spleen show increased levels of activation markers CD69 and CD71, compared to OVA-tolerized transgenic mice
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• markers (CD44high and CD62low) for memory T cell phenotypes are increased in CII-tolerized cells
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cellular
• 24 hours after exposure to 200 ug of CII tolerogen, T cells show a greatly reduced capacity to proliferate on CII stimulus compared to T cells from mice exposed to 200 ug of OVA; 48 hours after CII exposure, T cells are refractory to stimulation by CII peptide up to 130 uM
• after 72 hours, CII-tolerized cells can be stimulated by CII concentrations that are >2 logs higher than that needed to stimulate OVA-tolerized transgenic T cells
• suppressed proliferative response is observed up to 7 days post-CII treatment
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• when stimulated in vitro with CII (type II collagen) or a CII peptide, naive T cells show a vigorous proliferative response, while non-transgenic T cells do not
• proliferation of CII-tolerized T cells can be restored when cultured with CII and very high Il2 concentrations
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