[PDF][PDF] How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets

M Feuerer, Y Shen, DR Littman, C Benoist, D Mathis - Immunity, 2009 - cell.com
M Feuerer, Y Shen, DR Littman, C Benoist, D Mathis
Immunity, 2009cell.com
Summary CD4+ Foxp3+ regulatory T cells (Treg cells) are known to control the progression
of autoimmune diabetes, but when, where, and how they exert their influence in this context
are questions still under vigorous debate. Exploiting a transgene encoding the human
diphtheria toxin receptor, we punctually and specifically ablated Foxp3+ cells in the BCD2.
5/NOD mouse model of autoimmune diabetes. Strikingly, overt disease developed within 3
days. The earliest detectable event was the activation of natural killer (NK) cells directly …
Summary
CD4+Foxp3+ regulatory T cells (Treg cells) are known to control the progression of autoimmune diabetes, but when, where, and how they exert their influence in this context are questions still under vigorous debate. Exploiting a transgene encoding the human diphtheria toxin receptor, we punctually and specifically ablated Foxp3+ cells in the BCD2.5/NOD mouse model of autoimmune diabetes. Strikingly, overt disease developed within 3 days. The earliest detectable event was the activation of natural killer (NK) cells directly within the insulitic lesion, particularly the induction of Ifng gene expression within 7 hours of Treg cell ablation. Interferon-γ had a strong impact on the gene-expression program of the local CD4+ T effector cell population, unleashing it to aggressively attack the islets, which was required for the development of diabetes. Thus, Treg cells regulate pancreatic autoimmunity in situ through control of a central innate immune system player, NK cells.
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