Zhang, Yan; Yan, Ada Wc; Boelen, Lies; Hadcocks, Linda; Salam, Arafa; Gispert, Daniel Padrosa; Spanos, Loiza; Bitria, Laura Mora; Nemat-Gorgani, Neda; Traherne, James A; +9 more... Roberts, Chrissy; Koftori, Danai; Taylor, Graham P; Forton, Daniel; Norman, Paul J; Marsh, Steven Ge; Busch, Robert; Macallan, Derek C; Asquith, Becca; (2023) KIR-HLA interactions extend human CD8+ T cell lifespan in vivo. The Journal of clinical investigation, 133 (12). e169496. ISSN 0021-9738 DOI: https://doi.org/10.1172/JCI169496
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Abstract
BACKGROUNDThere is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo.METHODSWe used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections.RESULTSWe showed that an individual's iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype.CONCLUSIONSTogether, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.FUNDINGWellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
PubMed ID | 37071474 |
Elements ID | 201839 |
Official URL | http://dx.doi.org/10.1172/jci169496 |
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