The CD7- subset fo CD4+ memory T cells is prone to accelerated apoptosis that is prevented by interleukin-15 (IL-15)

Abstract

The CD7- subset of CD4+ T cells reflects a stable differentiation state of post-thymic helper T cells with CD45RO+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.