Related Experiment Video

Updated: Aug 9, 2026

Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
13:18

Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells

Published on: December 29, 2012

Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 and IL-12

L Rodella1, R Rezzani, G Zauli

  • 1Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy.

International Immunology
|July 25, 1998
PubMed

Insights

Interleukin-2 (IL-2) and Interleukin-12 (IL-12) cytokines enhance Natural Killer (NK) cell apoptosis-inducing activity. Cytokine-stimulated NK cells utilize both granzyme and Fas-FasL pathways for target cell death.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Natural Killer (NK) cells are crucial for innate immunity, eliminating target cells through cytotoxic mechanisms.
  • NK cell-mediated cytotoxicity involves granule exocytosis (perforins, granzymes) inducing necrosis or apoptosis, and Fas-FasL interactions triggering apoptosis.
  • Interleukins like IL-2 and IL-12 are known modulators of NK cell function.

Purpose of the Study:

  • To investigate the impact of IL-2 and IL-12 on the apoptosis-inducing capacity of NK cells.
  • To compare the effects of these cytokines on NK-sensitive (K562) and NK-insensitive (Raji) target cells.
  • To elucidate the specific pathways utilized by cytokine-stimulated NK cells for apoptosis induction.

Main Methods:

  • Co-culture of human peripheral blood NK cells with K562 and Raji target cells at varying effector:target ratios.
  • Treatment of NK cells with IL-2 and IL-12 prior to co-culture.
  • Assessment of target cell apoptosis using standard assays.
  • Analysis of NK cell cytotoxic mechanisms, including granzyme and Fas-FasL pathway involvement.

Main Results:

  • Apoptosis induction by NK cells is most effective at low target:effector ratios.
  • Resting NK cells exhibit minimal apoptosis-inducing activity.
  • IL-2 stimulation significantly enhances NK cell apoptosis induction against both target cell types.
  • IL-12 further augments the apoptosis-inducing capacity of IL-2-stimulated NK cells.
  • Cytokine-activated NK cells employ both granzyme and Fas-FasL pathways to induce target cell apoptosis.

Conclusions:

  • IL-2 and IL-12 are potent inducers of NK cell-mediated apoptosis.
  • The effectiveness of NK cell-induced apoptosis is dependent on the target:effector ratio.
  • Cytokine-primed NK cells utilize a dual mechanism involving granzymes and Fas-FasL for efficient target cell elimination.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia05:24

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia

Published on: February 21, 2021

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...