Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus

• DOI: 10.1007/s00018-023-05010-4
• Publication Date: 2024-01-12T05:02:03Z
• Authors: Katina D. Hulme; Zhen Wei Marcus Tong; Louise C. Rowntree; Carolien E. van d...; Katharina Ronacher; Emma J. Grant; Emily S. Dorey; Linda A. Gallo; Stephanie Gras; Katherine Kedzierska; Helen L. Barrett; Kirsty R. Short
• Keywords: Ionomycin

Abstract Diabetes mellitus is on the rise globally and a known susceptibility factor for severe influenza virus infections. However, mechanisms by which diabetes increases severity of an infection are yet to be fully defined. hallmarked high glucose concentrations in blood. We hypothesized that these affect functionality CD8 + T cells, play key role eliminating virus-infected cells have been shown decrease disease severity. To study effect hyperglycemia cell function, we stimulated peripheral blood mononuclear (PBMCs) from donors with without A virus, anti-CD3/anti-CD28-coated beads, PMA ionomycin (PMA/I), or viral peptide pool. After stimulation, were assessed [as defined expression IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1β, lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed increasing HbA1c correlated reduction TNF-α production response stimulation TCR-specific manner. This was not associated any changes subsets. conclude impairs function infection, may linked increased risk patients diabetes.