Humanized in vivo Model for Autoimmune Diabetes
Annual rept. 8 Jan 2009-7 Jan 2010
BENAROYA RESEARCH INST SEATTLE WA
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We previously reported now published, 2009 that two human GAD65 555-567-responsive T cell receptors TcRs expressed in HLA DR0401 transgenic mice exhibit different mechanisms of self-tolerance. 164 TcR transgenic mice evoke tolerance by strong thymic negative selection and peripheral activation-induced cell death AICD. 4.13 TcR transgenic mice select the TcR transgene near normal thymic cellularity levels and in the periphery result as a combination of IFN -secreting Th1 cells and IL-10-secreting Tr1 cells. Through crosses onto IL-10 knockout mice, we now have preliminary evidence that the regulatory cytokine IL-10 is maintaining an unactivated phenotype in 4.13 mice, which is in contrast to the self-antigenactivated phenotype observed in T cells from 164 mice.
- Anatomy and Physiology
- Medicine and Medical Research