CD95 ligand mediates T-cell receptor-induced apoptosis of a CD4+ CD8+ double positive thymic lymphoma.
Tumors in the thymus can be of different cellular origin. Among the most common tumors are thymoma and lymphoma, which are derived from transformed thymic epithelial cells and transformed lymphocytes, respectively. Thymic lymphoma and their response to apoptotic stimuli are poorly characterized. Here, we analyse apoptosis events in the thymic lymphoma cell line Thy278, which expresses cell surface antigens characteristic of immature double positive thymocytes. Upon T-cell receptor (TCR)/CD3 stimulation, Thy278 cells die by apoptosis, similar as primary thymocytes during negative selection. Caspases are crucial for deletion of both Thy278 cells and normal thymocytes. Moreover, we show that deletion of primary thymocytes and Thy278 cells upon CD3 stimulation is considerably impaired by neutralizing CD95L antibody. Thus, our results not only demonstrate that TCR-induced apoptosis is still functional in transformed thymocytes, but also suggest that Thy278 cells are a helpful model for the molecular analysis of negative selection.
Schmitz
I
I
Institute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany. ingo-schmitz@uni-duesseldorf.de
Meyer
C
C
Schulze-Osthoff
K
K
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016827:CD8 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D017637:Clonal Deletion; D053222:Fas Ligand Protein / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014176:Protein Biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology
D017252:CD3 Complex; D016827:CD8 Antigens; D053222:Fas Ligand Protein; D011948:Receptors, Antigen, T-Cell; D020169:Caspases