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- Title
A Humanized Mouse Model of Autoimmune Insulitis.
- Authors
Viehmann Milam, Ashley A.; Maher, Stephen E.; Gibson, Joanna A.; Lebastchi, Jasmin; Li Wen; Ruddle, Nancy H.; Herold, Kevan C.; Bothwell, Alfred L. M.
- Abstract
Many mechanisms of and treatments for type 1 diabetes studied in the NOD mouse model have not been replicated in human disease models. Thus, the field of diabetes research remains hindered by the lack of an in vivo system in which to study the development and onset of autoimmune diabetes. To this end, we characterized a system using human CD4+ T cells pulsed with autoantigen-derived peptides. Six weeks after injection of as few as 0.5 x 106 antigen-pulsed cells into the NOD-Scid II2rg-/- mouse expressing the human HLA-DR4 transgene, infitration of mouse islets by human T cells was seen. Although islet infiltration occurred with both healthy and diabetic donor antigen-pulsed CD4+ T cells, diabetic donor injections yielded significantly greater levels of insulitis. Additionally, significantly reduced insulin staining was observed in mice injected with CD4+ T-cell lines from diabetic donors. Increased levels of demethylated β-cell--derived DNA in the bloodstream accompanied this loss of insulin staining. Together, these data show that injection of small numbers of autoantigen-reactive CD4+ T cells can cause a targeted, destructive infiltration of pancreatic β-cells. This model may be valuable for understanding mechanisms of induction of human diabetes.
- Subjects
HUMAN T cells; PEPTIDES; AUTOANTIGENS; TRANSGENE expression; PANCREATIC beta cells; LABORATORY mice
- Publication
Diabetes, 2014, Vol 63, Issue 5, p1712
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db13-1141