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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
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Helper T cells down-regulate CD4 expression upon chronic stimulation giving rise to double-negative T cells
Inna V Grishkan1, Achilles Ntranos, Peter A Calabresi
1Department of Neurology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD, USA.
Cellular Immunology
|August 13, 2013
Summary
Researchers developed a new method to generate double-negative T (DNT) cells in vitro. This study suggests immune hyper-activation may drive DNT cell accumulation in certain diseases.
Area of Science:
- Immunology
- Cell Biology
Background:
- Double-negative T (DNT) cells (CD4(-)CD8(-)) are a subset of T cells with unclear developmental origins and pathological roles.
- DNT cell accumulation is observed in conditions like autoimmune lymphoproliferative syndrome and systemic lupus erythematosus.
Purpose of the Study:
- To investigate a novel in vitro method for generating DNT cells.
- To explore the potential link between immune hyper-activation and DNT cell generation.
Main Methods:
- Chronic in vitro stimulation of CD4(+) T cells to mimic immune hyper-activation.
- Flow cytometry analysis to characterize cell populations (CD3, CD4, CD8, NK1.1, TCR).
- Assessment of T cell receptor (TCR) stimulation dependency for survival.
Main Results:
- A CD3(+)CD4(-) population, identified as DNT cells, emerged after 4-5 rounds of stimulation.
- These DNT cells exhibited an effector phenotype, proliferated extensively, and required TCR stimulation for survival.
- The cells expressed MHC class II-restricted αβTCR, confirming their CD4(+) T cell origin.
Conclusions:
- This study presents a novel in vitro method for generating DNT cells from CD4(+) T cells.
- Immune hyper-activation is proposed as a potential in vivo mechanism contributing to the development of disease-associated DNT cells.
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