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

Yan Zhang; Ada W C Yan; Lies Boelen; Robert Busch; Derek Macallan; Becca Asquith

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

Yan Zhang, Ada W C Yan, Lies Boelen, Robert Busch, Derek Macallan, Becca Asquith

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	Journal of Experimental Medicine
Publication status	Submitted - 4 Jan 2023

Cite this

@article{0b31bcfe1e9c41ab8ebb250587cb73b8,

title = "KIR-HLA interactions extend human CD8+ T cell lifespan in vivo",

abstract = "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{\textquoteright}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.",

author = "Yan Zhang and Yan, {Ada W C} and Lies Boelen and Robert Busch and Derek Macallan and Becca Asquith",

note = "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.",

year = "2023",

month = jan,

day = "4",

language = "English",

journal = "Journal of Experimental Medicine",

issn = "1349-3329",

}

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 -