CD45 REGULATES APOPTOSIS INDUCED BY EXTRACELLULAR ADENOSINE-TRIPHOSPHATE AND CYTOTOXIC T-LYMPHOCYTES

Several lines of evidence implicate protein tyrosine phosphatases (PTP ) in the regulation of apoptotic cell death. We have evaluated the rol e of CD45, the major PTP of hematopoietic cells, in apoptosis induced by extracellular ATP (ATP(e)) and cytotoxic T lymphocytes (CTL). We ob served that two CD45(-) clones obtained by mutagenesis of the Fas(-) c ell line L1210, exhibit a higher susceptibility to apoptosis induced b y ATP(e), which was also evident in Ca2+-free conditions, when compare d to the parental cell line or CD45(+) variants. The CD45(-) cells wer e also more susceptible to death mediated by an alloreactive CTL clone . When the cytotoxic assay was performed in the presence of EGTA, a Ca 2+ chelator, which prevents cytotoxic granule exocytosis and perforin polymerization on target cell membranes, only the CD45(-) target cells were killed by the CTL clone. These results suggest that a cytotoxic pathway other than the secretory or Fas-dependent pathways was respons ible for the enhanced susceptibility of CD45(-) cells to death, and th erefore provide further evidence for the role of ATP, as a possible me diator of Ca2+-independent cell destruction by CTL. (C) 1996 Academic Press, Inc.