%0 Journal Article
%A Zhang, Y
%A Yan, AWC
%A Boelen, L
%A Hadcocks, L
%A Salam, A
%A Gispert, DP
%A Spanos, L
%A Bitria, LM
%A Nemat-Gorgani, N
%A Traherne, JA
%A Roberts, C
%A Koftori, D
%A Taylor, GP
%A Forton, D
%A Norman, PJ
%A Marsh, SGE
%A Busch, R
%A Macallan, DC
%A Asquith, B
%D 2023
%F discovery:10174707
%I American Society for Clinical Investigation
%J Journal of Clinical Investigation
%N 12
%T KIR-HLA interactions extend human CD8+ T cell lifespan in vivo
%U https://discovery.ucl.ac.uk/id/eprint/10174707/
%V 133
%X 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+ 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+ 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+ 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. CONCLUSIONS. Together, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.
%Z © 2023 Zhang et al. This work is licensed under the Creative Commons Attribution 4.0 International License  (http://creativecommons.org/licenses/by/4.0/).