Ultrastructural and functional studies of the interaction between IL-12 and IL-2 for the generation of lymphokine-activated killer cells

Paola Facchetti, Carlo Tacchetti, Ignazia Prigione, Irma Airoldi, Anna Favre, Carlo Enrico Grossi, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

IL-12 promotes generation of LAK activity in short-term-cultured NK cells, but information on the structure and function of IL.12-induced LAK cells is not yet available. The latter issues have been here investigated with emphasis on interactions between IL-12 and IL-2. Peripheral blood mononuclear cells (MNC) exposed to IL-12 for 5-7 days displayed a decrease in the amount and density of the matrix of large granular lymphocyte (LGL)- associated granules. In cells cultured with IL-12 and IL.2 for 5-7 days, empty vacuoles were predominant and the electron-dense matrix was scanty. In MNC incubated with IL-2 for 5-7 days, most granules were loaded with electron-dense matrix. IL-12 and IL-2 displayed an additive effect on LAK cell cytotoxicity until approximately 48 h in culture which was followed by a sharp decline. Immunocytochemical and biochemical studies demonstrated that MNC cultured for 5-7 days with IL-12 and IL-2 displayed downregulated perforin expression and upregulated gran-zyme B expression. Fas ligand expression was virtually undetectable in MNC cultured for 5-7 days with or without cytokines. It appears that perforin downregulation plays a major role in the reduced cytotoxicity of MNC cultured with IL-12 and IL-2 for 5-7 days.

Original languageEnglish
Pages (from-to)440-453
Number of pages14
JournalExperimental Cell Research
Volume253
Issue number2
DOIs
Publication statusPublished - Dec 15 1999

Keywords

  • Cytokines
  • Cytotoxicity
  • Human NK cells

ASJC Scopus subject areas

  • Cell Biology

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