6533b836fe1ef96bd12a1392

RESEARCH PRODUCT

Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2

Hermann WagnerMartin RöllinghoffDonald BunjesConny Hardt

subject

Cytotoxicity ImmunologicT-LymphocytesImmunologyCyclosporinsPharmacologyBiologyLymphocyte ActivationMiceInterleukin 21Cyclosporin aAnimalsImmunology and AllergyInterleukin 5Interleukin 4Interleukin 3Mice Inbred BALB CProteinsInterleukinInterleukin 33Protein BiosynthesisMice Inbred CBAInterleukin 12Interleukin-2Lymphocyte Culture Test MixedImmunosuppressive AgentsInterleukin-1

description

The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.

https://doi.org/10.1002/eji.1830110812