A new study that was led by scientists at the La Jolla Institute for Immunology showed that healthy people can have predatory CD8+ T cells in their pancreases, and in high numbers.
Type 1 diabetes (T1D) develops when the body’s own immune system destroys the pancreatic beta cells. Breakdown in peripheral tolerance and compromised thymic selection have been thought to be associated with the development of T1D. However, the results of a recent study challenge this belief.Researchers found that CD8+ T cells that target preproinsulin (PPI, an insulin precursor) exist in high numbers peripherally and the pancreas of both healthy people and those with T1D. Pancreas samples were obtained from donors with short-term and long-standing diabetes and patients without diabetes. In situ immunofluorescence staining of antigen-specific CD8 T cells in pancreatic tissue sections and images, the analysis was performed. The results showed that abundant PPI-specific CD8+ T cells are found in the human exocrine pancreas of people with and without T1D.
The data suggest that T1D does not develop due to abnormal T cell function leading to a beta cell attack. Therefore, another process or factor triggers the T cell attack on the pancreas. However, the study results did indicate that there were more CD8+ T cells in donors with T1D than those without diabetes. The researchers hypothesize that the increase of the CD8+ T cells in those with T1D may be due to inflammatory triggers. The accumulation of proinsulin from beta cell metabolic stress may result in beta cell recognition and destruction.
Taken together, the results challenge the position that systemic immune regulatory mechanisms or a defective thymic selection of CD8 T cells are the main basis of T1D pathogenesis. The presence of PPI-reactive CD8+ T cells in the peripheral blood may be the normal or default state, and events occurring locally in the pancreas make the difference between maintaining a healthy state and the development of T1D. Given the new insight regarding CD8+ T cells in the exocrine pancreas, a beta cell-directed approach to developing a therapy for T1D may provide more effective treatments for T1D.
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Diabetes researchers spot dangerous T cells in the pancreas—even in healthy people. (2020). Retrieved 4 November 2020, from https://medicalxpress.com/news/2020-10-diabetes-dangerous-cells-pancreaseven-healthy.html