A role for calcineurin in degranulation of murine cytotoxic T lymphocytes

J. P. Dutz, D. A. Fruman, S. J. Burakoff, B. E. Bierer

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


The immunosuppressive drugs cyclosporin A (CsA) and FK506 bind to distinct families of intracellular proteins, cyclophilins, and FK506 binding proteins (FKBP) respectively, termed immunophilins. Immunosuppressant-immunophilin complexes bind to and inhibit the activity of calcineurin, a calcium- dependent serine/threonine phosphatase. CsA is known to inhibit degranulation in CTL as assessed by N benzyloxylcarbonyl-L-lysine thiobenzyl ester- esterase release assays. We have investigated whether calcineurin phosphatase activity is involved in this degranulation. Both CsA and FK506 are shown to inhibit N benzyloxylcarbonyl-L-lysine thiobenzyl ester-esterase release in murine CTL clones induced either by cognate target or by PMA and the calcium ionophore A23187. Inhibition is concentration dependent and is observed at drug concentrations that specifically inhibit cellular calcineurin. The FK506-binding immunophilin FKBP12, as well as calcineurin, are shown to be present in these cells by immunoblotting analysis. Rapamycin, a macrolide antibiotic thought to compete with FK506 for binding to common FKBP receptor sites, antagonizes the effects of FK506 on both degranulation and calcineurin activity. Neither the degranulation nor the effect of the immunosuppressants is affected by the protein synthesis inhibitor cycloheximide. These observations suggest a role for calcineurin in CTL degranulation. Thus, in addition to its previously described role in lymphokine gene activation, calcineurin also appears to be involved in T cell activation processes which do not require protein synthesis.

Original languageEnglish
Pages (from-to)2591-2598
Number of pages8
JournalJournal of Immunology
Issue number7
StatePublished - 1993
Externally publishedYes


Dive into the research topics of 'A role for calcineurin in degranulation of murine cytotoxic T lymphocytes'. Together they form a unique fingerprint.

Cite this