Phorbol Ester-Induced Reversible Inactivation of Cytotoxic T Cell Function: Correlation with Down-Regulation of Protein Kinase C Activity

Hitoshi Ohmori, Toshitaka Shimada, Masaki Hikida, Toshiyuki Takai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

When an H-2d-specific cytotoxic T lymphocytes (CTL) clone, FC1, was incubated in the presence of 10-7 M phorbol myristate acetate (PMA) for 10-12 hr, the cytolytic activity of the CTL against H-2d target cells was abrogated, but was reversibly restored to the normal level after subsequent incubation of the cells in PMA-free medium for more than 10 hr. These effects of PMA have been reported (Russell, J.H.: J. Immunol. 133, 907- 912 (1984)), but the mode of its action has not been fully investigated. Here, we analyzed the biochemical basis of the PMA-induced loss of cytolytic activity. Cycloheximide completely blocked the restoration of the PMA-suppressed cytolytic activity, suggesting that protein synthesis was required in this process. PMA-treatment did not affect the levels of CD3 and CD8 molecules expressed on the CTL, nor was the level of a CTL-specific serine esterase, BLT esterase, affected by this treatment. However, the target cell-induced release of BLT esterase from the CTL was suppressed if the cells were pretreated with PMA. PMA-treatment of the CTL led to the down-regulation of protein kinase C (PKC) activity by about 50%. On the other hand, staurosporin, an inhibitor of PKC, completely blocked the target cell lysis when added at 10-M. These results suggest that the down-regulation of at least some isoform(s) of PKC is responsible for the PMA-induced loss of the cytotolytic activity of CTL.

Original languageEnglish
Pages (from-to)427-432
Number of pages6
JournalJapanese Journal of Pharmacology
Volume66
Issue number4
DOIs
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • Cytotoxic T cell
  • Phorbol ester
  • Protein kinase C
  • Serine esterase
  • Target cell lysis

ASJC Scopus subject areas

  • Pharmacology

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