Humanized in vivo Model for Autoimmune Diabetes
Abstract
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 and/or 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA625335
Entities
People
- Gerald T. Nepom
- John A. Gebe
Organizations
- Benaroya Research Institute