Identification of low molecular weight probes on perforin- and fas-based killing mediated by cytotoxic T lymphocytes

Perforin- and Fas-based killing pathways are two major mechanisms of cytotoxic T lymphocytes (CTL)-mediated cytotoxicity, In this paper, we have reported the identification of low molecular weight probes on CTL-mediated cytolysis, In addition to inhibitors of acidification so far reported, three other groups of compounds hare been identified to block perforin-based cytolysis by the CD8(+) CTL clone: (1) an inhibitor of actin polymerization (cytochalasin D), (2) respiratory inhibitors (antimycin A and oligomycin A), and (3) protein kinase inhibitors (calphostin C, herbimycin A, B252a, and staurosporine). Since Fas-based cytolysis by CD4(+) CTL clone was inhibitable or rather increased by these agents, only vacuolar type H+-ATPase inhibitors such as concanamycin A have been shown to be highly specific probes to block perforin-based CTL-mediated cytotoxicity.