Protective role of IL-2 during activation of T cells with bryostatin 1

Ferdynand J. Kos, David L. Cornell, Anne B. Lipke, Laura J. Graham, Harry D. Bear

Research output: Contribution to journalArticlepeer-review

Abstract

Pharmacologic agents such as bryostatin 1 (bryostatin) can regulate cell activation, growth, and differentiation by modulating the activities of protein kinase C isoenzymes. Inhibition of growth of tumor cells and activation of T lymphocytes in vitro are the most recognized consequences of bryostatin treatment. The effect of bryostatin on T cells ranges from induction of apoptotic cell death to T cell activation, expansion, and acquisition of antigen-specific effector functions. Here, we describe the conditions under which these wide ranging effects occur. Mouse mammary tumor 4TO7-IL-2-primed lymph node cells exposed ex vivo to bryostatin upregulated CD25 expression but lost the ability to secrete IL-2. Most of these cells died by apoptosis unless IL-2 was provided for the duration of bryostatin treatment. Analysis of T cell repertoire by screening of T cells for the expression of different Vβ T cell receptor (TCR) families revealed that bryostatin-induced T cell death was unbiased and Vβ-nonspecific. Within particular Vβ clones, only CD25+ T cells survived exposure to bryostatin and IL-2. Treatment of 4TO7 tumor-bearing mice with a single injection of low dose bryostatin followed by multiple low doses of IL-2, but not with bryostatin alone, delayed tumor growth. These results indicate that activation of T cells with bryostatin should be carried out under protection of exogenous IL-2 to ensure survival and expansion of T cells that may exhibit anti-tumor activity. Copyright (C) 2000 International Society for Immunopharmacology.

Original languageEnglish (US)
Pages (from-to)645-652
Number of pages8
JournalInternational Journal of Immunopharmacology
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2000

Keywords

  • Bryostatin
  • CD25
  • IL-2
  • T cell activation
  • Tumor immunotherapy

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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