Apoptosis of thymic lymphoma clones by thymic epithelial cells: a putative model for 'death by neglect'.
We have previously described an in vitro system in which thymic epithelial cells induce apoptosis in CD4+ 8+ thymocytes or thymic lymphoma cells, in the absence of an exogenous antigen. A thymic epithelial cell line (TEC) recapitulated the response, by inducing apoptosis in CD4+ 8+ thymocytes of the thymic lymphoma clone, PD1.6. The present study pursues the involvement of the T-cell receptor (TcR) in the response of PD1.6 to TEC. TcR cross-linking did not cause apoptosis of PD1.6, although it induced tyrosine phosphorylation of p95vav. In contrast, TEC did not induce phosphorylation of p95vav but induced apoptosis of PD1.6 cells. These results suggest that TcR-evoked signals are not involved in TEC-induced apoptosis of PD1.6. Intracellular calcium chelation, using BAPTA-loaded PD1.6 cells, diminished TEC-induced apoptosis. Protein kinase C depletion in PD1.6 cells augmented their apoptotic response to TEC. Thus, the response of PD1.6 to TEC is calcium-dependent and inhibited by PKC. Likewise, the apoptotic response of PD1.6 to A23187 was abrogated by PKC activation. PD1.6 cells may represent an immature double positive thymocyte population, which does not undergo negative selection. The interaction of PD1.6 with TEC may thus serve as a model for the TcR-independent 'Death by Neglect', which takes place in the thymus during thymocyte development.
Zilberman
Y
Y
Department of Pharmacology, The Faculty of Dental Medicine Founded by the Alpha-Omega Fraternity, The Hebrew University, Jerusalem, Israel.
Yefenof
E
E
Katzav
S
S
Dorogin
A
A
Rosenheimer-Goudsmid
N
N
Guy
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D018920:Coculture Techniques / Q000379:methods; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D016399:Lymphoma, T-Cell; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D013950:Thymus Gland
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002413:Cations, Divalent; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; D011493:Protein Kinase C; D002118:Calcium