Related Experiment Video

Updated: Jun 30, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

p47phox-deficient immune microenvironment signals dysregulate naive T-cell apoptosis

M Donaldson1, A Antignani, J Milner

  • 1Monocyte Trafficking Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-145, USA.

Cell Death and Differentiation
|September 23, 2008
PubMed

Insights

Phagocyte NADPH oxidase deficiency in mice causes lymphoid hyperplasia due to impaired CD8(+) T cell apoptosis. In vitro, these cells show survival defects, but in vivo, lymph node microenvironments promote lymphocyte accumulation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Medicine

Background:

  • Phagocyte NADPH oxidase is crucial for microbial killing.
  • Deficiency in p47(phox) subunit causes chronic granulomatous disease (CGD).
  • CGD is associated with immune dysregulation.

Purpose of the Study:

  • To investigate the impact of p47(phox) deficiency on lymphocyte populations and survival.
  • To elucidate the mechanisms underlying lymphoid hyperplasia in p47(phox-/-) mice.
  • To explore the role of microenvironmental factors in lymphocyte homeostasis.

Main Methods:

  • Analysis of lymphocyte populations (T and B cells) in lymph nodes of p47(phox-/-) and wild-type mice.
  • In vitro culture of lymphocytes to assess apoptosis, gene expression (Bim, Puma, Bcl-2), and mitochondrial function.
  • Treatment of cultured lymphocytes with IL-7 and glucose oxidase to evaluate survival rescue.

Main Results:

  • p47(phox-/-) mice exhibit lymph node hyperplasia with increased naive T and B cells and altered T:B cell ratios.
  • Cultured p47(phox-/-) CD8(+) T lymphocytes show increased apoptosis, linked to Bim/Puma upregulation and Bcl-2 downregulation.
  • IL-7 and hydrogen peroxide partially improve survival of cultured p47(phox-/-) CD8(+) T cells, but not to wild-type levels.

Conclusions:

  • p47(phox-/-) CD8(+) T lymphocytes possess an intrinsic survival defect related to oxidase deficiency.
  • In vivo lymph node microenvironments in CGD mice contain factors that suppress apoptosis and promote lymphocyte accumulation.
  • Understanding these factors is key to explaining lymphoid hyperplasia in the context of NADPH oxidase deficiency.

More Related Videos

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes12:59

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 26, 2013

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets07:12

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

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.
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...