Apoptosis of thymic lymphoma clones by thymic epithelial cells: a putativemodel 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, i n 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 involvem ent 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 pho sphorylation of p95(vav). In contrast, TEC did not induce phosphorylation o f p95(vav), but induced apoptosis of PD1.6 cells. These results suggest tha t TcR-evoked signals are not involved in TEC-induced apoptosis of PD1.6. In tracellular calcium chelation, using BAPTA-loaded PD1.6 cells, diminished T EC-induced apoptosis. Protein kinase C depletion in PD1.6 cells augmented t heir apoptotic response to TEC. Thus, the response of PD1.6 to TEC is calci um-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 i mmature double positive thymocyte population, which does not undergo negati ve selection. The interaction of PD1.6 with TEC may thus serve as a model f or the TcR-independent 'Death by Neglect', which takes place in the thymus during thymocyte development. (C) 1999 Elsevier Science B.V. All rights res erved.