immune system
• mutant antigen presenting cells in mixed lymphocyte culture fail to suppress CTL-mediated lysis of allogenic cells in the presence of a soluble form of CD200 as occurs with wild-type APCs
• APC produce more IFN-gamma and less IL-4 in the presence of soluble CD200 in these mixed lymphocyte cultures
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• mutant bone marrow derived dendritic cells become polarized in vitro to induce antigen specific T regulatory cells when cultured with soluble CD200
• in vivo infusion of soluble CD200 for 4 weeks also leads to polarization of dendritic cells to induce T regulatory cells
• 4 x 106 dendritic cells isolated from mutant mice that received soluble CD200 for 4 weeks are able to significantly prolong allogenic skin graft survival when transferred to C57BL/6 hosts
• these tolerogenic dendritic cells no longer suppress skin graft rejection if cells are cultured with LPS or a mixture of TNF and IFN-gamma before being transfered into allograft hosts
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• splenocytes cultured for 24 hours in the absence of any stimulus produce significantly more IL-12p40 than wild-type splenocytes
• IL-12p40 secretion remains significantly higher by splenocytes in the presence of LPS-stimulation
• LPS-induced IL-12p40 production by splenocytes is not suppressed by a soluble form of CD200 compared to controls where there is a 65% suppression
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• splenocytes cultured for 24 hours in the absence of any stimulus produce significantly more TNF than wild-type splenocytes
• TNF secretion remains significantly higher by splenocytes in the presence of LPS-stimulation
• LPS-induced TNF production by splenocytes is not suppressed by a soluble form of CD200 compared to controls where there is a 65% suppression
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• a soluble form of CD200 fails to prolong skin allograft survival in mutant recipient mice as it does in wild-type recipient mice
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