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
dc.contributor.author | Nandedkar-Kulkarni, Neha | |
dc.contributor.author | Esakov, Emily | |
dc.contributor.author | Gregg, Brigid | |
dc.contributor.author | Atkinson, Mark A. | |
dc.contributor.author | Rogers, Douglas G. | |
dc.contributor.author | Horner, James D. | |
dc.contributor.author | Singer, Kanakadurga | |
dc.contributor.author | Lundy, Steven K. | |
dc.contributor.author | Felton, Jamie L. | |
dc.contributor.author | Al-Huniti, Tasneem | |
dc.contributor.author | Kalinoski, Andrea Nestor | |
dc.contributor.author | Morran, Michael P. | |
dc.contributor.author | Gupta, Nirdesh K. | |
dc.contributor.author | Bretz, James D. | |
dc.contributor.author | Balaji, Swapnaa | |
dc.contributor.author | Chen, Tian | |
dc.contributor.author | McInerney, Marcia F. | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2023-06-13T09:26:26Z | |
dc.date.available | 2023-06-13T09:26:26Z | |
dc.date.issued | 2021 | |
dc.description.abstract | 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 β 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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Nandedkar-Kulkarni N, Esakov E, Gregg B, et al. 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. 2021;206(7):1443-1453. doi:10.4049/jimmunol.1900357 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/33697 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Association of Immunologists | en_US |
dc.relation.isversionof | 10.4049/jimmunol.1900357 | en_US |
dc.relation.journal | The Journal of Immunology | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Type 1 diabetes mellitus | en_US |
dc.subject | Insulin-secreting cells | en_US |
dc.subject | Pancreas | en_US |
dc.subject | Insulin receptor | en_US |
dc.subject | T-Lymphocytes | en_US |
dc.title | 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 | en_US |
dc.type | Article | en_US |