Cyclosporin-A inhibits IL-2 production by all human T-cell clones having this function, independent of the T4 T8 phenotype or the coexpression of cytolytic activity

Silvano Ferrini, Alessandro Moretta, Roberto Biassoni, Angelo Nicolin, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

Cyclosporin A (CsA) is an immunosuppressive drug that acts, at least in part, by blocking IL-2 release. Since IL-2-producing human T cells are heterogeneous with respect to their functional capabilities and surface phenotype, we investigated whether differences in sensitivity to CsA existed among different IL-2-producing T-cell clones. Preliminary dose/response experiments showed that 100 ng/ml CsA completely inhibited the PHA- or OKT3-induced IL-2 production by four representative T4+ T8- clones. On the other hand, this drug concentration had virtually no inhibitory effect on the proliferation of CTL-L murine indicator cells to exogeneous IL-2. Clones were derived directly from peripheral blood by applying a microculture system that allows clonal expansion of essentially all T cells: under these experimental conditions growing clones are therefore highly representative of the starting T-cell populations. Among clones so derived, 28 were selected according to their capability to release IL-2 upon PHA stimulation. Six of such clones displayed cytolytic activity in a PHA-dependent assay against P815 murine target cells. CsA (100 ng/ml) abrogated IL-2 production of all clones, including those displaying cytolytic activity and expressing the T4- T8+ phenotype.

Original languageEnglish
Pages (from-to)79-84
Number of pages6
JournalClinical Immunology and Immunopathology
Volume38
Issue number1
DOIs
Publication statusPublished - 1986

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

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