The CD7(-) subset of CD4(+) memory T cells is prone to accelerated apoptosis that is prevented by interleukin-15 (IL-15).
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-alpha stimulated fibroblasts that expose membrane IL-15. TNF-alpha 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.
Rappl
G
G
Department of Dermatology, The Saarland University Hospital, Homburg/Saar; Germany.
Abken
H
H
Hasselmann
D O
DO
Tilgen
W
W
Ugurel
S
S
Reinhold
U
U
D019011:Antigens, CD7 / Q000032:analysis*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D003872:Dermatitis / Q000276:immunology*; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D019011:Antigens, CD7; C508024:IL15RA protein, human; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor