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

Bioscience, Biotechnology, and Biochemistry
T KataokaK Nagai

Abstract

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 have 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, K252a, 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.

Citations

Apr 9, 2020·Frontiers in Cellular and Infection Microbiology·Swati GargShailja Singh
Dec 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jianfei QianQing Yi

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