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Updated: Jun 30, 2026
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
Summary
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.
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