TY  - JOUR
TI  - KIR-HLA interactions extend human CD8+ T cell lifespan in vivo
AV  - public
VL  - 133
Y1  - 2023///
IS  - 12
N1  - © 2023 Zhang et al. This work is licensed under the Creative Commons Attribution 4.0 International License  (http://creativecommons.org/licenses/by/4.0/).
N2  - 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.
ID  - discovery10174707
PB  - American Society for Clinical Investigation
UR  - https://doi.org/10.1172/JCI169496
JF  - Journal of Clinical Investigation
A1  - Zhang, Y
A1  - Yan, AWC
A1  - Boelen, L
A1  - Hadcocks, L
A1  - Salam, A
A1  - Gispert, DP
A1  - Spanos, L
A1  - Bitria, LM
A1  - Nemat-Gorgani, N
A1  - Traherne, JA
A1  - Roberts, C
A1  - Koftori, D
A1  - Taylor, GP
A1  - Forton, D
A1  - Norman, PJ
A1  - Marsh, SGE
A1  - Busch, R
A1  - Macallan, DC
A1  - Asquith, B
ER  -