{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:06:40Z","timestamp":1792613200954,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Efforts to eradicate tuberculosis (TB) are threatened by diabetes mellitus (DM), which confers a 3-fold increase in the risk of TB disease. The changes in the memory phenotypes and functional profiles of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>)-specific T cells in latent TB infection (LTBI)-DM participants remain poorly characterised. We, therefore, assessed the effect of DM on T-cell phenotype and function in LTBI and DM clinical groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the memory phenotypes and function profiles of <jats:italic>Mtb<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells among participants with LTBI-DM (n=21), LTBI-only (n=17) and DM-only (n=16). Peripheral blood mononuclear cells (PBMCs) were stimulated with early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) peptide pools or phytohemagglutinin (PHA). The memory phenotypes (CCR7\/CD45RA), and functional profiles (HLA-DR, PD-1, CD107a, IFN-\u03b3, IL-2, TNF, IL-13, IL-17A) of <jats:italic>Mtb<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells were characterised by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Na\u00efve CD4<jats:sup>+<\/jats:sup> T cells were significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.47 (0.34-0.69) vs 0.91 (0.59-1.05); (p&amp;lt;0.001)]. Similarly, CD8<jats:sup>+<\/jats:sup> HLA-DR expression was significantly decreased in LTBI-DM compared to LTBI-only participants [0.26 (0.19-0.33) vs 0.52 (0.40-0.64); (p&amp;lt;0.0001)], whereas CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> PD-1 expression was significantly upregulated in the LTBI-DM compared to the LTBI-only participants [0.61 (0.53-0.77) vs 0.19 (0.10-0.28); (p&amp;lt;0.0001) and 0.41 (0.37-0.56) vs 0.29 (0.17-0.42); (p=0.007)] respectively. CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> IFN-\u03b3 production was significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.28 (0.19-0.38) vs 0.39 (0.25-0.53); (p=0.030) and 0.36 (0.27-0.49) vs 0.55 (0.41-0.88); (p=0.016)] respectively. CD4<jats:sup>+<\/jats:sup> TNF and CD8<jats:sup>+<\/jats:sup> IL-17A production were significantly decreased in participants with LTBI-DM compared to those with LTBI-only [0.38 (0.33-0.50) vs 0.62 (0.46-0.87); (p=0.004) and 0.29 (0.16-0.42) vs 0.47 (0.29-0.52); (0.017)] respectively. LTBI-DM participants had significantly lower dual-functional (IFN-\u03b3<jats:sup>+<\/jats:sup>IL-2<jats:sup>+<\/jats:sup> and IL-2<jats:sup>+<\/jats:sup>TNF<jats:sup>+<\/jats:sup>) and mono-functional (IFN-\u03b3<jats:sup>+<\/jats:sup> and TNF<jats:sup>+<\/jats:sup>) CD4<jats:sup>+<\/jats:sup> responses than LTBI-only participants. LTBI-DM participants had significantly decreased dual-functional (IFN-\u03b3<jats:sup>+<\/jats:sup>IL-2<jats:sup>+<\/jats:sup>, IFN-\u03b3<jats:sup>+<\/jats:sup> TNF<jats:sup>+<\/jats:sup> and IL-2<jats:sup>+<\/jats:sup>TNF<jats:sup>+<\/jats:sup>) and mono-functional (IFN-\u03b3<jats:sup>+<\/jats:sup>, IL-2<jats:sup>+<\/jats:sup> and TNF<jats:sup>+<\/jats:sup>) central and effector memory CD4<jats:sup>+<\/jats:sup> responses compared to LTBI-only participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Type 2 DM impairs the memory phenotypes and functional profiles of <jats:italic>Mtb<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells, potentially indicating underlying immunopathology towards increased active TB disease risk.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1480739","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T04:27:19Z","timestamp":1728016039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Impaired Mycobacterium tuberculosis-specific T-cell memory phenotypes and functional profiles among adults with type 2 diabetes mellitus in 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