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 role of CD45, the major PTP of hematopoietic cells, in apoptosis induced by extracellular ATP (ATP(e)) and cytotoxic T lymphocytes (CTL). We observed that two CD45(-) clones obtained by mutagenesis of the Fas(-) cell line L1210, exhibit a higher susceptibility to apoptosis induced by ATP(e), which was also evident in Ca2+-free conditions, when compared to the parental cell line or CD45(+) variants. The CD45(-) cells were also more susceptible to death mediated by an alloreactive CTL clone. When the cytotoxic assay was performed in the presence of EGTA, a Ca2+ 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 responsible for the enhanced susceptibility of CD45(-) cells to death, and therefore provide further evidence for the role of ATP, as a possible mediator of Ca2+-independent cell destruction by CTL. (C) 1996 Academic Press, Inc.