Immunosuppressants FK506 and rapamycin have different effects on the biosynthesis of cytoplasmic actin during the early period of T cell activation.

Molecular Hematology Branch, Section on Protein and RNA Biosynthesis, National Heart, Lung and Blood Institute, Bldg. 10, Room 7D18, Bethesda,MD 20892-21654, U.S.A.FK506 and rapamycin are immunosuppressants that interferewith T cell activation. FK506 inhibits early events of T cellactivation such as the induction of cytokine transcription,whereas rapamycin inhibits later interleukin 2 signalling events.However, both reagents either directly or indirectly reduceprotein synthesis. Therefore a kinetic study was conducted inhuman primary T lymphocytes examining increased synthesis ofproteins stimulated by either ionomycin›phorbol myristateacetate (PMA) or PMA alone. Three patterns of protein ex-pression were observed. Synthesis of one group of proteins hadenhanced synthesis with FK506, but reduced synthesis withrapamycin. A second group had reduced synthesis with rapa-mycinandeithernochangeoraslightreductionwithFK506anda third group had reduction with both FK506 and rapamycin.Onemajorproteinofthefirstgroup,p42,hadarapidincreasein