Publications by authors named "David J De George"
Chronic destruction of insulin-producing pancreatic β cells by T cells results in autoimmune diabetes. Similar to other chronic T cell-mediated pathologies, a role for T cell exhaustion has been identified in diabetes in humans and NOD mice. The development and differentiation of exhausted T cells depends on exposure to Ag.
View Article and Find Full Text PDFIntroduction: Chronic activation of self-reactive T cells with beta cell antigens results in the upregulation of immune checkpoint molecules that keep self-reactive T cells under control and delay beta cell destruction in autoimmune diabetes. Inhibiting PD1/PD-L1 signaling results in autoimmune diabetes in mice and humans with pre-existing autoimmunity against beta cells. However, it is not known if other immune checkpoint molecules, such as TIGIT, can also negatively regulate self-reactive T cells.
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- - Persistent exposure to antigens leads to the development of exhausted T cells, which are less effective in responding to threats, and this phenomenon typically occurs during chronic infections and cancer, raising questions about its role in autoimmune diabetes.
- - In a study using nonobese diabetic (NOD) mice, exhausted CD8+ T cells targeting the islet antigen IGRP were found in the pancreas, while more of these cells were preserved in peripheral lymphoid organs.
- - By creating transgenic NOD mice that express IGRP in cells outside the islet, researchers showed that exposure to IGRP in these extraislet areas resulted in severely exhausted T cells, which ultimately protected the mice from developing diabetes.
Type 1 diabetes is an autoimmune disease with onset from early childhood. The insulin-producing pancreatic beta cells are destroyed by CD8 cytotoxic T cells. The disease is challenging to study mechanistically in humans because it is not possible to biopsy the pancreatic islets and the disease is most active prior to the time of clinical diagnosis.
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- Immune checkpoint inhibitors can effectively treat cancer but are linked to immune-related side effects, including type 1 diabetes (T1D), prompting researchers to explore preventive treatments like JAK1/JAK2 inhibitors.* -
- In experiments with nonobese diabetic mice, JAK1/JAK2 inhibitors successfully prevented and even reversed diabetes caused by PD-L1 blockade, inhibiting harmful immune cell activity in the pancreas.* -
- The study demonstrates that JAK1/JAK2 inhibitors might be a viable option for managing diabetes resulting from cancer therapy, without compromising the anti-tumor effectiveness in other models.*
Interferon gamma (IFNγ) is a proinflammatory cytokine implicated in autoimmune diseases. However, deficiency or neutralization of IFNγ is ineffective in reducing disease. We characterize islet antigen-specific T cells in non-obese diabetic (NOD) mice lacking all three IFN receptor genes.
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