Unknown

Dataset Information

0

Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.


ABSTRACT: The surface receptor CD8α is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8α may impact critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models, compared to CD8α+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8α expression was induced on approximately 30% of previously CD8α- NK cells following IL-15 stimulation. These 'induced' CD8α+ ('iCD8α+') NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8α expression ('sustained CD8α+) or those that remained CD8α- ('persistent CD8α-'). These iCD8α+ cells originated from an IL-15Rβ high NK cell population, with CD8α expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8α status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors.

SUBMITTER: Cubitt CC 

PROVIDER: S-EPMC11291271 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

altmetric image

Publications


The surface receptor CD8α is present on 20%-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses in patients with leukemia in prior studies, thus, we hypothesized that CD8α may affect critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models compared with CD8α+ NK cells, likely due to an enhanced capacity fo  ...[more]

Similar Datasets

| S-EPMC2276384 | biostudies-literature
| S-EPMC10471975 | biostudies-literature
| S-EPMC7613074 | biostudies-literature
| S-EPMC5549915 | biostudies-literature
| S-EPMC9309064 | biostudies-literature
| S-EPMC6545784 | biostudies-literature
| S-EPMC3495902 | biostudies-other
| S-EPMC9768581 | biostudies-literature
| S-EPMC4239055 | biostudies-literature
| S-EPMC3520618 | biostudies-literature