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Related Experiment Videos

NK cells regulate CD8+ T cell effector function in response to an intracellular pathogen.

Ramakrishna Vankayalapati1, Peter Klucar, Benjamin Wizel

  • 1Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, 11937 US Highway 271, Tyler, TX 75708, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 23, 2003
PubMed
Summary

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Natural killer (NK) cells enhance CD8+ T cell responses against Mycobacterium tuberculosis. NK cells promote CD8+ T cell effector functions and lysis of infected cells, crucial for immunity.

Area of Science:

  • Immunology
  • Cellular Biology
  • Infectious Diseases

Background:

  • Mycobacterium tuberculosis (M. tuberculosis) infection poses a significant global health challenge.
  • CD8+ T cells are crucial for controlling intracellular pathogens, but their regulation is complex.
  • Natural killer (NK) cells are key players in innate immunity, with emerging roles in adaptive immunity.

Purpose of the Study:

  • To investigate the role of NK cells in regulating human CD8+ T cell effector function against M. tuberculosis-infected cells.
  • To elucidate the mechanisms by which NK cells influence M. tuberculosis-specific CD8+ T cell responses.

Main Methods:

  • Depletion of NK cells from peripheral blood mononuclear cells (PBMCs) of healthy tuberculin reactors.
  • Analysis of CD8+ T cell frequency and function (IFN-gamma production, cytotoxicity).

Related Experiment Videos

  • Assessment of cytokine production (IFN-gamma, IL-15, IL-18) by NK cells and monocytes.
  • Investigation of cell-cell contact-dependent mechanisms involving CD40 ligand (CD40L) and CD40.

    • Main Results:

    • NK cell depletion reduced M. tuberculosis-responsive CD8+IFN-gamma+ T cells and their cytotoxic capacity against infected monocytes.
    • Soluble factors from activated NK cells, including IFN-gamma, IL-15, and IL-18, restored CD8+ T cell frequency.
    • NK cells produced IFN-gamma, which stimulated infected monocytes to produce IL-15 and IL-18.
    • NK cell-mediated priming of CD8+ T cells required cell-cell contact via CD40L-CD40 interactions.

    Conclusions:

    • NK cells are essential for maintaining M. tuberculosis-responsive CD8+IFN-gamma+ T cells.
    • NK cells orchestrate CD8+ T cell responses through a cytokine network (IFN-gamma, IL-15, IL-18) and cell-cell contact.
    • NK cells bridge innate and adaptive immunity, optimizing CD8+ T cell functions critical for controlling M. tuberculosis and other intracellular pathogens.