Humanized in vivo Model for Autoimmune Diabetes
Annual rept. 8 Jan 2007-7 Jan 2008
BENAROYA RESEARCH INST SEATTLE WA
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The CD4 T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents major obstacles to improved therapies. This research study entails using humanized mice manifesting type 1 diabetes T1D-associated human HLA molecules to address the fate and pathogenicity of high and low avidity T cells reactive to the putative autoantigen glutamic acid decarboxylase 65 GAD65. By modeling the dominant human anti-GAD65 response in HLA- and TCR-transgenic mice, we proposed to determine whether pathogenic andor regulatory responses correspond to high or low avidity profiles at different points during disease course. These ongoing studies indicate that the tolerance mechanisms used to prevent self-antigen GAD65 reactive T cells from eliciting autoimmunity in humanized DR4 HLA mice are diverse and that no single mechanism is exclusively used to maintain immune tolerance and prevent diabetes.
- Medicine and Medical Research