1. KIR-HLA interactions extend human [CD8.sup.+] T cell lifespan in vivo
- Author
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Zhang, Yan, Yan, Ada W.C., Boelen, Lies, Hadcocks, Linda, Salam, Arafa, Gispert, Daniel Padrosa, Spanos, Loiza, Bitria, Laura Mora, Nemat-Gorgani, Neda, Traherne, James A., Roberts, Chrissy, Koftori, Danai, Taylor, Graham P., Forton, Daniel, Norman, Paul J., Marsh, Steven G.E., Busch, Robert, Macallan, Derek C., and Asquith, Becca
- Subjects
CD8 lymphocytes -- Health aspects -- Physiological aspects ,Glycoproteins -- Health aspects -- Physiological aspects ,Immunological research ,HLA histocompatibility antigens -- Health aspects -- Physiological aspects ,Immune response -- Research ,Cell interaction -- Research ,Histocompatibility antigens -- Health aspects -- Physiological aspects ,Health care industry - Abstract
BACKGROUND. There 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.sup.+] 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. METHODS. We used stable isotope labeling with deuterated water to quantify memory [CD8.sup.+] T cell survival in healthy individuals and patients with chronic viral infections. RESULTS. We showed that an individual's iKIR-ligand genotype was a significant determinant of [CD8.sup.+] T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory [CD8.sup.+] T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory [CD8.sup.+] 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.sup.+] and [CD4.sup.+] T cell immune aging phenotype. CONCLUSIONS. Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival. FUNDING. Wellcome 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., Introduction The human killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors. They are expressed predominantly by NK cells but are also found on T cells [...]
- Published
- 2023
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