TY - JOUR
T1 - KIR-HLA interactions extend human CD8+ T cell lifespan in vivo
AU - Zhang, Yan
AU - Yan, Ada W C
AU - Boelen, Lies
AU - Busch, Robert
AU - Macallan, Derek
AU - Asquith, Becca
N1 - I have listed only first and last three authors; the attached file has the full list.
The first three authors contributed equally, and the last three authors contributed equally, as noted in the ms.
Previously submitted to Sci Immunol on 15 Dec.
PY - 2023/1/4
Y1 - 2023/1/4
N2 - 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 virus infection and that these results are consistent with an increase in CD8+ T cell lifespan due to iKIR-ligand interactions. Here we test this prediction and investigate whether iKIRs affect T cell lifespan in humans in vivo. We used stable isotope labelling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. We show that an individual’s iKIR-ligand genotype is a significant determinant of CD8+ T cell lifespan: in individuals with two iKIR-ligand gene pairs, memory CD8+ T cells survive on average for 125 days, in individuals with four iKIR-ligand gene pairs then memory CD8+ T cell lifespan is doubled to 250 days. Additionally, we show that this survival advantage is independent of iKIR expression by the T cell of interest and further that iKIR-ligand genotype alters CD8+ and CD4+ T cell immune aging phenotype. Together these data reveal an unexpectedly large impact of iKIR genotype on T cell survival.
AB - 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 virus infection and that these results are consistent with an increase in CD8+ T cell lifespan due to iKIR-ligand interactions. Here we test this prediction and investigate whether iKIRs affect T cell lifespan in humans in vivo. We used stable isotope labelling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. We show that an individual’s iKIR-ligand genotype is a significant determinant of CD8+ T cell lifespan: in individuals with two iKIR-ligand gene pairs, memory CD8+ T cells survive on average for 125 days, in individuals with four iKIR-ligand gene pairs then memory CD8+ T cell lifespan is doubled to 250 days. Additionally, we show that this survival advantage is independent of iKIR expression by the T cell of interest and further that iKIR-ligand genotype alters CD8+ and CD4+ T cell immune aging phenotype. Together these data reveal an unexpectedly large impact of iKIR genotype on T cell survival.
M3 - Article
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 1349-3329
ER -