First Author | Nandedkar-Kulkarni N | Year | 2021 |
Journal | J Immunol | Volume | 206 |
Issue | 7 | Pages | 1443-1453 |
PubMed ID | 33658296 | Mgi Jnum | J:303894 |
Mgi Id | MGI:6515407 | Doi | 10.4049/jimmunol.1900357 |
Citation | Nandedkar-Kulkarni N, et al. (2021) Insulin Receptor-Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice. J Immunol 206(7):1443-1453 |
abstractText | Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell-mediated autoimmune destruction of insulin-producing pancreatic beta cells occurs. In previous work, when purified IR(+) and IR(-) T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR(+) T cells developed insulitis and diabetes. In this study, peripheral blood samples from individuals with T1D (new onset to 14 y of duration), relatives at high-risk for T1D, defined by positivity for islet autoantibodies, and healthy controls were examined for frequency of IR(+) T cells. High-risk individuals had significantly higher numbers of IR(+) T cells as compared with those with T1D (p < 0.01) and controls (p < 0.001); however, the percentage of IR(+) T cells in circulation did not differ significantly between T1D and control subjects. With the hypothesis that IR(+) T cells traffic to the pancreas in T1D, we developed a (to our knowledge) novel mouse model exhibiting a FLAG-tagged mouse IR on T cells on the C57BL/6 background, which is not susceptible to developing T1D. Interestingly, these C57BL/6-CD3FLAGmIR/mfm mice showed evidence of increased IR(+) T cell trafficking into the islets compared with C57BL/6 controls (p < 0.001). This transgenic animal model provides a (to our knowledge) novel platform for investigating the influence of IR expression on T cell trafficking and the development of insulitis. |