Humanized in vivo Model for Autoimmune Diabetes

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2010
Accession Number
ADA523882

Entities

People

  • Gerald T. Nepom

Organizations

  • Benaroya Research Institute

Tags

DTIC Thesaurus Topics

  • Antigens
  • Autoimmune Diseases
  • Biological Sciences
  • Blood
  • Boundaries
  • Cell Physiological Processes
  • Cells
  • Contrast
  • Cytokines
  • Glutamic Acid
  • Lymph Nodes
  • Lymphatic System
  • Lymphocytes
  • Molecules
  • Phenotypes
  • Thymocytes
  • Tissues

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology