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Updated: Apr 20, 2026

Isolation of Double Negative αβ T Cells from the Kidney
Published on: May 16, 2014
Double negative (DN) αβ T cells: misperception and overdue recognition
Maria N Martina1, Sanjeev Noel2, Ankit Saxena2
11] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Double negative (DN) T cells are normal immune cells, not just abnormal ones. Impaired Fas-mediated apoptosis causes their accumulation, suggesting a new model for their role in the immune system.
Area of Science:
- Immunology
- Cell Biology
- T cell biology
Background:
- CD4(-)CD8(-) double-negative (DN) αβ T cells are normal immune cells but are poorly understood.
- Their association with lymphoproliferative disorders (like autoimmune lymphoproliferative syndromes) has led to them being viewed as abnormal.
- The traditional model suggests these abnormal DN T cells arise from CD4 or CD8 T cells losing coreceptors.
Purpose of the Study:
- To challenge the traditional view of abnormal DN T cells in lymphoproliferation.
- To propose a new model for the origin and regulation of DN T cells.
- To stimulate discussion and research into normal DN T cells (nDN T cells).
Main Methods:
- Revisiting the traditional model of abnormal DN T cells (lpr DN T cells) in light of recent immunological advances.
- Proposing a new model for DN T cell homeostasis.
- Analyzing the role of Fas-mediated apoptosis in regulating DN T cell populations.
Main Results:
- The traditional model of lpr DN T cells is critically re-evaluated and found to be flawed.
- A new model is proposed: Fas-mediated apoptosis normally removes peripheral DN T cells.
- Impaired Fas-mediated apoptosis leads to the accumulation of existing DN T cells, not their de novo generation.
Conclusions:
- The origin of lpr DN T cells and their regulation by the Fas pathway require re-evaluation.
- Normal DN T cells (nDN T cells) are an important cell type warranting further investigation.
- The Fas pathway plays a crucial role in the homeostasis of normal DN T cells.
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