CD95/Fas-triggered apoptosis of activated T lymphocytes is prevented by dendritic cells through a CD58-dependent mechanism.
T-cell apoptosis is a mechanism regulating T-cell homeostasis. Activation renders T cells susceptible to activation-induced cell death, a process mediated through CD95 ligand/CD95 (Apo-1/Fas) ligation. The aim of this study was to test whether antigen-presenting cells can inhibit CD95/Fas-triggered activation-induced cell death. Dendritic cells (DC), which are highly effective antigen-presenting cells, were generated in vitro from human peripheral blood monocytes by culture in granulocyte-macrophage colony-stimulating factor and interleukin 4. Subsequently, DC were cocultured with activated T cells and the effect of DC on CD95/Fas-mediated apoptosis was determined. Coculture with increasing amounts of DC prevented CD95/Fas-triggered apoptosis in a dose-dependent fashion by inhibiting activation of caspase 8 and caspase 3. This protective effect of the DC on T-cell death could be blocked by 50% by adding an anti-CD58 antibody, whereas further addition of anti-CD80 (B7.1) and anti-CD86 (B7.2) led to an even more pronounced effect. Our findings suggest that DC can protect T cells from activation-induced cell death, with CD58 ligation playing a key role.
Daniel
P T
PT
Department of Hematology, Oncology and Tumorimmunology, Charité, Campus Berlin-Buch, Robert-Rössle Klinik, Humboldt Universität, Berlin, Germany. pdaniel@mdc-berlin.de
Scholz
C
C
Essmann
F
F
Westermann
J
J
Pezzutto
A
A
Dörken
B
B
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D018968:CD58 Antigens / Q000502:physiology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D009000:Monocytes / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018968:CD58 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D019014:fas Receptor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases