CD8α marks a Mycobacterium tuberculosis-reactive human NK cell population with high activation potential Journal Article


Authors: Mehanna, N.; Pradhan, A.; Kaur, R.; Kontopoulos, T.; Rosati, B.; Carlson, D.; Cheung, N. K. V.; Xu, H.; Bean, J.; Hsu, K. C.; Le Luduec, J. B.; Vorkas, C. K.
Article Title: CD8α marks a Mycobacterium tuberculosis-reactive human NK cell population with high activation potential
Abstract: Natural Killer (NK) cells can recognize and kill Mycobacterium tuberculosis (Mtb)-infected cells in vitro, however their role after natural human exposure has not been well-studied. To identify Mtb-responsive NK cell populations, we analyzed the peripheral blood of healthy household contacts of active Tuberculosis (TB) cases and source community donors in an endemic region of Port-au-Prince, Haiti by flow cytometry. We observed higher CD8α expression on NK cells in putative resistors (Interferon γ release assay negative; IGRA− contacts) with a loss of CD8α surface expression during household-associated exposure and active TB disease. In vitro assays and CITE-seq analysis of CD8α+ NK cells demonstrated enhanced maturity, cytotoxic gene expression, and response to cytokine stimulation relative to CD8α− NK cells. CD8α+ NK cells also displayed dynamic surface expression dependent on MHC class I in contrast to conventional CD8+ T cells. Together, these results support a specialized role for CD8α+ NK cell populations during Mtb infection correlating with disease resistance. © The Author(s) 2025.
Keywords: adult; cd8 antigen; metabolism; immunology; lymphocyte activation; mycobacterium tuberculosis; natural killer cell; killer cells, natural; microbiology; tuberculosis; humans; human; male; female; cd8 antigens
Journal Title: Scientific Reports
Volume: 15
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2025-04-29
Start Page: 15095
Language: English
DOI: 10.1038/s41598-025-98367-4
PUBMED: 40301594
PROVIDER: scopus
PMCID: PMC12041513
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    650 Cheung
  2. James M Bean
    24 Bean
  3. Katharine C Hsu
    184 Hsu
  4. Hong Xu
    54 Xu