Zhang, Y;
Yan, AWC;
Boelen, L;
Hadcocks, L;
Salam, A;
Gispert, DP;
Spanos, L;
... Asquith, B; + view all
(2023)
KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.
Journal of Clinical Investigation
, 133
(12)
, Article e169496. 10.1172/JCI169496.
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KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.pdf - Published Version Download (3MB) | Preview |
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+ 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.
| Type: | Article |
|---|---|
| Title: | KIR-HLA interactions extend human CD8+ T cell lifespan in vivo |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI169496 |
| Publisher version: | https://doi.org/10.1172/JCI169496 |
| Language: | English |
| Additional information: | © 2023 Zhang et al. This work is licensed under the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10174707 |
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