Molecular and biological actions of cyclosporin A and FK506 on T cell development and function.
The microbial products cyclosporin A (CsA) and FK506 are potent immunosuppressive agents in experimental and clinical transplantation. Binding of both drugs to intracellular immunophilins results in the inhibition of calcineurin activity and the prevention of interleukin-2 gene transcription and, thus, in the inhibition of T cell receptor-dependent T cell activation. CsA and FK506 also have a profound effect on the structure and function of the thymus with disruption of positive and negative selection of T cells. These influences on thymic microenvironment and T cell ontogeny disrupt the induction or maintenance of self-tolerance (or both) and are thus of relevance to clinical transplantation immunology.
Holländer
G A
GA
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Bierer
B E
BE
Burakoff
S J
SJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology