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T-cell control of IL-12p75 production.
1Ghost Lab, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. kabdi@niaid.nih.gov
Scandinavian Journal of Immunology
|July 27, 2006
Summary
Early immune responses involve the p40 subunit of interleukin-12 (IL-12), not the complete IL-12p75 heterodimer. Dendritic cells require specific conditioning for IL-12p75 production, challenging its role as an initial immune trigger.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-12 (IL-12) is considered a pro-inflammatory cytokine produced by dendritic cells (DCs) early in immune responses.
- It is thought to bridge innate and adaptive immunity, particularly after stimulation by bacterial pathogens or lipopolysaccharide (LPS).
Purpose of the Study:
- To investigate the specific forms of IL-12 secreted by dendritic cells in response to LPS.
- To determine the conditions required for the production of the bioactive IL-12p75 heterodimer.
Main Methods:
- Stimulation of dendritic cells with lipopolysaccharide (LPS).
- Analysis of secreted IL-12 subunits (p40 and IL-12p75) using biochemical assays.
- Investigation of T cell and microbial product effects on IL-12 production.
- Assessment of dendritic cell conditioning by interferon-gamma (IFN-gamma) or activated T cells.
Main Results:
- Dendritic cells secreted large amounts of the IL-12 p40 subunit, but not the IL-12p75 heterodimer, early after LPS stimulation.
- Neither naive T cells nor microbial products induced IL-12p75 production.
- Dendritic cell conditioning with IFN-gamma or activated T cells was necessary for IL-12p75 induction.
Conclusions:
- The early, copious secretion in response to LPS is primarily the IL-12 p40 subunit, not the functional IL-12p75 heterodimer.
- The inability of naive T cells and bacterial products to induce IL-12p75 suggests it does not initiate early innate and adaptive immune responses as previously thought.