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ResearchIn-Press PreviewImmunology
Open Access | 10.1172/JCI173602
1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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Tran, J.
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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1Division of Oncology, Washington Univerity School of Medicine, St. Louis, United States of America
2Division of Oncology, Washington University School of Medicine, St. Louis, United States of America
3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
4Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, United States of America
5Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, United States of America
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Published May 28, 2024 - More info
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.