The development of humanized mouse models to study immune regulation of autoreactive T cells. (BA15P.229)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.179-179.13
• Main Authors: Aryee, Ken-Edwin, Brehm, Michael
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.179.13

Type 1 diabetes (T1D) is the immune mediated destruction of insulin-producing beta cells in the pancreas, characterized by the loss of peripheral tolerance mechanisms needed to prevent autoimmunity. Regulatory T-cells (TREG) are a specialized CD4 T cell subset important for maintaining peripheral tolerance. IL-2 is critical to maintain TREG fitness and function, and deficiencies in the IL-2 receptor and signaling pathways contribute to the development of T1D. The lack of an in vivo system that fully recapitulates human T1D development impairs the ability to study the role of IL-2 signaling in T1D. Here we show that the Hu-PBL-SCID humanized mouse model can be used to study effector T cells and TREG from T1D-individuals. For these studies we injected PBMC from T1D or non-T1D donors into NOD Rag1null IL2rγnull (NRG) mice and followed the engraftment of human T cell populations. Our results show that PBMC from T1D donors engraft NRG mice with similar kinetics as compared to non-T1D donors. Moreover, our preliminary data show that expression of human IL-2 in recipient NRG mice improves T1D TREG frequency and survival. These results indicate that humanized mice are an effective model for studying autoreactive T cells from diabetic individuals