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

Katina D Hulme; Zhen Wei Marcus Tong; Louise C Rowntree; Carolien E van de Sandt; Katharina Ronacher; Emma J Grant; Emily S Dorey; Linda A Gallo; Stephanie Gras; Katherine Kedzierska; Helen L Barrett; Kirsty R Short

doi:10.1007/s00018-023-05010-4

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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

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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

Katina D Hulme, Zhen Wei Marcus Tong, Louise C Rowntree, Carolien E van de Sandt, Katharina Ronacher, Emma J Grant, Emily S Dorey, Linda A Gallo, Stephanie Gras, Katherine Kedzierska, …

Cellular and Molecular Life Sciences, Vol.81, pp.1-11

2024

DOI: https://doi.org/10.1007/s00018-023-05010-4

PMCID: PMC10786977

PMID: 38214784

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Abstract

adaptive immune response

T cell receptor complex

hyperglycemia

high glucose

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

Details

Title: 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
Authors: Katina D Hulme (Author) - The University of Queensland
Zhen Wei Marcus Tong (Author) - The University of Queensland
Louise C Rowntree (Author) - Peter Doherty Institute
Carolien E van de Sandt (Author) - Peter Doherty Institute
Katharina Ronacher (Author) - The University of Queensland
Emma J Grant (Author) - La Trobe University
Emily S Dorey (Author) - Mater Research
Linda A Gallo (Author) - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
Stephanie Gras (Author) - La Trobe University
Katherine Kedzierska (Author) - Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia
Helen L Barrett (Author) - Mater Health Services
Kirsty R Short (Corresponding Author) - The University of Queensland
Publication details: Cellular and Molecular Life Sciences, Vol.81, pp.1-11
Publisher: Birkhaeuser Science
Date published: 2024
DOI: 10.1007/s00018-023-05010-4
ISSN: 1420-9071
PMID: 38214784; PMC10786977
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Data Availability: The data sets generated during the current study are not publicly available due to nature of the ethical approvals. If you have a reasonable request, please contact the corresponding author.
Grants: The investigation of an unconventional Human Leukocyte Antigen molecule, DE210101479, Australian Research Council (Australia, Canberra) - ARC
Organisation Unit: School of Health - Biomedicine
Language: English
Record Identifier: 99999998602621
Output Type: Journal article

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