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Cytokine-mediated communication between dendritic epidermal T cells and Langerhans cells. In vitro studies using cell
K Yokota1, K Ariizumi, T Kitajima
1Department of Dermatology, University of Texas South-Western Medical Center, Dallas 75235, USA.
Insights
Dendritic epidermal T cells (DETC) promote Langerhans cell (LC) proliferation via secreted GM-CSF and CSF-1. This interaction suggests a mutual regulatory role for these immune cells in the murine epidermis.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Murine epidermis harbors Langerhans cells (LC), a dendritic cell (DC) lineage, and dendritic epidermal T cells (DETC), a gamma delta T cell subset.
- The functional crosstalk between LC and DETC in vivo remains largely unexplored despite their close proximity.
Purpose of the Study:
- To investigate the functional interaction between LC and DETC using established cell lines.
- To identify the specific factors mediating DETC-induced LC proliferation.
Main Methods:
- Coculture of the DC line XS52 with the DETC line 7-17.
- Analysis of XS52 DC proliferation in response to DETC and DETC-derived supernatants.
- Inhibition assays using antibodies against specific cytokines (GM-CSF, CSF-1) and cytokine screening.
Main Results:
- XS52 DC exhibited maximal proliferation when cocultured with 7-17 DETC or their activated supernatants.
- DETC-induced DC proliferation was significantly inhibited by antibodies against granulocyte/macrophage colony-stimulating factor (GM-CSF) and CSF-1 receptor (CD115).
- GM-CSF, CSF-1, IL-4, and IL-13 were identified as significant growth promoters for XS52 DC; IL-4 was not implicated in the DETC-DC interaction.
Conclusions:
- GM-CSF and CSF-1 secreted by DETC are key mediators of LC proliferation.
- Coculture with DC induced DETC to secrete GM-CSF and CSF-1 and enhanced their responsiveness to IL-15.
- These findings suggest a reciprocal regulatory mechanism between LC and DETC in the epidermis.
Abstract:
Murine epidermis contains two leukocyte populations: Langerhans cells (LC), which are APC of dendritic cell (DC) lineage, and dendritic epidermal T cells (DETC), which are members of the tissue-type gamma delta T cell family. Despite close physical approximation in vivo, the extent to which LC and DETC affect each other's function has remained unknown. We addressed this question using the long term DC line XS52 and the gamma delta T cell line 7-17, both of which were established from mouse epidermis, and both of which retain important features of the resident populations from which they were derived. XS52 DC proliferated maximally when cocultured with gamma-irradiated 7-17 DETC. They also proliferated in response to culture supernatants collected from anti-CD3- or Con A-activated 7-17 DETC, but not from nonstimulated DETC. In both systems, DETC-induced XS52 DC growth was inhibited partially (up to 70%) by Abs against granulocyte/macrophage CSF (GM-CSF) or CD115 (CSF-1 receptor) and nearly completely (up to 90%) by both together. Among 28 tested cytokines, only GM-CSF, CSF-1, IL-4, and IL-13 promoted XS52 DC growth significantly. Anti-IL-4 failed to inhibit DETC-induced XS52 cell growth, and IL-4 was not detectable in DETC supernatants. Thus, we conclude that GM-CSF and CSF-1 (and perhaps IL-13) account for the DC growth-promoting activity secreted by DETC. These results suggest that during coculture, XS52 DC activate 7-17 DETC to secrete both GM-CSF and CSF-1. In fact, when cultured with XS52 DC, 7-17 DETC also elevated their expression of the gamma c receptor and acquired proliferative responsiveness to their own growth factor IL-15. We propose that LC and DETC in situ may interact with each other in a similar manner, thereby regulating their residence and function.