| First Author | Zhao Y | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 399 |
| Issue | 4 | Pages | 629-36 |
| PubMed ID | 20691153 | Mgi Jnum | J:164900 |
| Mgi Id | MGI:4835606 | Doi | 10.1016/j.bbrc.2010.07.128 |
| Citation | Zhao Y, et al. (2010) Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model. Biochem Biophys Res Commun 399(4):629-36 |
| abstractText | Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing beta cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rgamma(null) mice. The selective destruction of pancreatic islet beta cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total beta-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the beta cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet beta cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4(+) T cell infiltration and clonal expansion, and the mouse islet beta-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet beta cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D. |
