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

Area of Science:

• Immunology
• Infectious Diseases
• Cell Biology

Background:

• Natural Killer (NK) cells possess the ability to eliminate Mycobacterium tuberculosis (Mtb)-infected cells in laboratory settings.
• The precise role of NK cells in human immunity following natural Mtb exposure remains largely uncharacterized.

Purpose of the Study:

• To investigate Mtb-responsive NK cell populations in individuals exposed to Tuberculosis (TB).
• To elucidate the function and characteristics of specific NK cell subsets in the context of Mtb infection and disease resistance.

Main Methods:

• Peripheral blood samples from healthy household contacts of active TB cases and community donors in an endemic region were analyzed using flow cytometry.
• In vitro assays and CITE-seq analysis were performed on CD8α+ NK cells to assess their maturity, cytotoxic potential, and cytokine responsiveness.

Main Results:

• Higher CD8α expression on NK cells was observed in individuals presumed to be resistant to TB (Interferon-γ release assay negative).
• A decrease in CD8α surface expression on NK cells was noted during household exposure to TB and in active TB disease.
• CD8α+ NK cells exhibited increased maturity, enhanced cytotoxic gene expression, and a heightened response to cytokine stimulation compared to CD8α- NK cells.
• CD8α+ NK cell surface expression dynamics were found to be dependent on MHC class I, differing from conventional CD8+ T cells.

Conclusions:

• Specialized CD8α+ NK cell populations play a significant role in the immune response to Mtb infection.
• The characteristics and behavior of CD8α+ NK cells correlate with resistance to TB disease, highlighting their potential as immune biomarkers.