CHARACTERIZATION OF LPR-DERIVED T-CELL HYBRIDOMAS - FAS-DEFICIENT HYBRIDOMAS ARE DEATHLESS, GROWTH-ARRESTED, AND CYTOTOXIC UPON ACTIVATION

T cell hybridomas that are deathless upon TCR crosslinking were genera ted from lpr mice. The deathless hybridomas (1.4 and 5D5) expressed ex tremely low Fas even after anti-CD3 activation, whereas activation-ind uced cell death (AICD) was observed for Fas-expressing hybridomas. The deathless hybridomas were activated to produce Fast and IL-2, indicat ing that the intrinsic defect in Fas expression or up-regulation resul ted in AICD blockade. The deathless hybridoma cells expressed longer a nd stronger Fast cytotoxicity than AICD-sensitive hybridomas, Although deathless, activated 5D5 cells were arrested at the G1/S border. Grow th arrest lasted for at least 5 days, but some cells eventually recove red and proliferated. The deathless 5D5 cells were used to demonstrate that AICD includes a fratricidal mechanism that kills AICD-sensitive bystanders, The deathless T cell hybridomas are useful tools for study ing T cell activation-dependent functions sensitive to AICD. (C) 1996 Academic Press, Inc.