Abstract
The CD7− subset of CD4+ T cells reflects a stable differentiation state of post-thymic helper T cells with CD45R0+CD45RA− ‘memory’ phenotype. Here we report that CD4+CD7− T cells are prone to increased spontaneous apoptosis in vitro compared to CD4+CD7+ T cells. Spontaneous apoptosis is prevented by IL-15, but not by IL-2. Moreover, IL-15 increases Bcl-2 and decreases CD95/Fas expression of CD7−, but not of CD7+ T cells. Because IL-15 is physiologically not secreted but expressed in a membrane-bound form, we cocultured T cells with TNF-α stimulated fibroblasts that expose membrane IL-15. TNF-α stimulated fibroblasts rescue CD4+CD7− T cells from apoptosis whereas unstimulated fibroblasts do not. Rescue from apoptosis requires cell-cell contact and is abolished by addition of neutralizing antibodies to IL-15. We conclude that membrane IL-15 prevents accelerated apoptosis of CD4+CD7− T cells. This mechanism may contribute to accumulation of CD7− T cells in chronic inflammatory skin lesions.
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Abbreviations
- FACS:
-
fluorescence-activated cell sorter
- MFI:
-
mean fluorescence intensity
- TUNEL:
-
terminal deoxynucleotidyl transferase reaction
- PI:
-
propidium iodide
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Acknowledgements
We would like to thank Mrs S Maas, P Hofmann and A Cremer for technical assistance and supplying dermal fibroblasts and Dr S Bulfone-Paus (Berlin) for supplying us with the anti-IL-15 antibody. This work was supported by the Fritz-Bender-Stiftung, Munich, (H Abken) and by the Deutsche Forschungsgemeinschaft, Bonn (Re690/4-2, U Reinhold).
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Rappl, G., Abken, H., Hasselmann, D. et al. The CD7− subset of CD4+ memory T cells is prone to accelerated apoptosis that is prevented by interleukin-15 (IL-15). Cell Death Differ 8, 395–402 (2001). https://doi.org/10.1038/sj.cdd.4400825
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DOI: https://doi.org/10.1038/sj.cdd.4400825
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