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, PDL6. 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 PDL6, although it induced tyrosine phosphorylation of p95(vav). In contrast, TEC did not induce phosphorylation of p95(vav), but induced apoptosis of PDL6 cells. These results suggest that TcR-evoked signals are not involved in TEC-induced apoptosis of PDL6. Intracellular calcium chelation, using BAPTA-loaded PDL6 cells, diminished TEC-induced apoptosis. Protein kinase C depletion in PDL6 cells augmented their apoptotic response to TEC. Thus, the response of PDL6 to TEC is calcium-dependent and inhibited by PKC. Likewise, the apoptotic response of PDL6 to A23187 was abrogated by PKC activation. PDL6 cells may represent an immature double positive thymocyte population, which does not undergo negative selection. The interaction of PDL6 with TEC may thus serve as a model for the TcR-independent 'Death by Neglect', which takes place in the thymus during thymocyte development.