KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.

Autor:	Zhang Y; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom., Yan AW; Department of Infectious Disease, Imperial College London, London, United Kingdom., Boelen L; Department of Infectious Disease, Imperial College London, London, United Kingdom., Hadcocks L; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom., Salam A; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom., Gispert DP; Department of Infectious Disease, Imperial College London, London, United Kingdom., Spanos L; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom.; School of Life and Health Sciences, University of Roehampton, London, United Kingdom., Bitria LM; Department of Infectious Disease, Imperial College London, London, United Kingdom., Nemat-Gorgani N; Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA., Traherne JA; Department of Pathology, University of Cambridge, Cambridge, United Kingdom., Roberts C; Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom., Koftori D; Department of Infectious Disease, Imperial College London, London, United Kingdom., Taylor GP; Department of Infectious Disease, Imperial College London, London, United Kingdom.; National Centre for Human Retrovirology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom., Forton D; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom.; Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom., Norman PJ; Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.; Department of Biomedical Informatics and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Marsh SG; Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom.; UCL Cancer Institute, UCL, London, United Kingdom., Busch R; School of Life and Health Sciences, University of Roehampton, London, United Kingdom., Macallan DC; Institute for Infection and Immunity, St George's, University of London, London, United Kingdom., Asquith B; Department of Infectious Disease, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2023 Jun 15; Vol. 133 (12). Date of Electronic Publication: 2023 Jun 15.
DOI:	10.1172/JCI169496
Abstrakt:	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.
Databáze:	MEDLINE
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