A calcium- and perforin-independent pathway of killing mediated by murine cytolytic lymphocytes

John Ding E. Young, William R. Clark, Chad Ching Liu, Zanvil A. Cohn

Research output: Contribution to journalJournal Article peer-review

67 Scopus citations

Abstract

Cytotoxic T lymphocytes have been thought to lyse cellular targets in the past by a calcium-dependent pathway. This notion was recently supported by the identification and purification of a pore-forming protein (perforin) from the granules of these cell types. Here, we show that perforin is absent from a number of cell lines that nevertheless display vigorous cytolytic activity toward target cells. The cytotoxic activity of eight murine CTL lines is completely or partially retained in the absence of calcium. The calcium-independent lytic activity is associated with two subcellular fraction peaks isolated by Percoll gradient centrifugation, e.g., a heavy density band migrating with granule markers and a lighter band corresponding to free cytosolic material. These results suggest a complex picture of lymphocyte-mediated killing involving probably multiple mechanisms and mediators that may operate in concert or independently in the delivery of the lethal hit.
Original languageEnglish
Pages (from-to)1894-1899
Number of pages6
JournalJournal of Experimental Medicine
Volume166
Issue number6
DOIs
StatePublished - 01 12 1987
Externally publishedYes

Keywords

  • Animal
  • Calcium
  • Cell Line
  • Cytotoxicity, Immunologic
  • Immunity, Cellular
  • In Vitro
  • Membrane Proteins
  • Mice
  • Support, Non-U.S. Gov't
  • Support, U.S. Gov't, P.H.S.
  • T-Lymphocytes, Cytotoxic

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