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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
CD4+ T lymphocyte subsets express connexin 43 and establish gap junction channel communication with macrophages in
Alexandra Bermudez-Fajardo1, Minna Ylihärsilä, W Howard Evans
1School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Insights
This study reveals that connexin 43 (Cx43) forms gap junctions between mouse CD4+ T lymphocytes and macrophages. This direct cell communication, crucial for immune regulation, is modulated by LPS and favors Th1-macrophage interactions.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Gap junction channels, formed by connexins (Cxs), are vital for lymphocyte functions like Ig and cytokine secretion, transmigration, and antigen cross-presentation.
- Cx43 expression is known in various cells, but its role in lymphocyte-macrophage communication was previously uncharacterized.
Purpose of the Study:
- To investigate the expression of Cx43 in mouse CD4+ T lymphocyte subpopulations (Th0, Th1, Th2).
- To demonstrate gap junction channel formation between lymphocytes and macrophages in vitro.
- To explore the modulation of this cell communication by lipopolysaccharide (LPS) and its dependence on T helper cell subset.
Main Methods:
- RT-PCR and Western blotting to detect Cx43 mRNA and protein in isolated CD4+ T lymphocyte subpopulations.
- In vitro co-culture assays to assess gap junction formation between lymphocytes and primary macrophages.
- Treatment with LPS to evaluate its effect on lymphocyte-macrophage communication.
Main Results:
- Cx43 mRNA and protein are expressed in mouse CD4+ Th0, Th1, and Th2 lymphocytes.
- Gap junction channels are formed between these lymphocytes and primary macrophages in vitro.
- Th1-macrophage interactions show a particular preference for this direct communication.
- LPS treatment inhibits lymphocyte-macrophage cross-talk, irrespective of the T helper cell subset.
Conclusions:
- Cx43 mediates direct communication between T lymphocytes and macrophages via gap junctions.
- This cell-cell communication is subject to modulation, as shown by LPS inhibition.
- Gap junction-mediated communication represents a novel mechanism potentially involved in immune regulation, independent of specific antigenic stimulation.
Abstract:
Gap junction channels constructed of connexins (Cxs) are expressed by peripheral and secondary lymphoid organ-derived lymphocytes. These channels in the plasma membrane play key roles in a range of lymphocyte functions exemplified by the synthesis and secretion of Igs and cytokines and during transmigration across the endothelium. Most recently, their involvement in antigen cross-presentation has also been established. We report here for the first time the expression of mRNA and protein encoding Cx43 in mouse-derived CD4+ Th0, Th1, and Th2 lymphocyte subpopulations and demonstrate the establishment gap junction channel formation with primary macrophages in vitro. We show that this mode of direct communication is particularly favored in Th1-macrophage interactions and that LPS inhibits lymphocyte-macrophage cross-talk independently of the subset of lymphocyte involved. Our work suggests that gap junction-mediated communication can be modulated in the absence of specific antigenic stimulation. Therefore, a further mechanism featuring gap junction-mediated communication may be implicated in immune regulation.
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