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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.

Original publication

DOI

10.1016/0955-3886(94)90133-3

Type

Journal article

Journal

Transfus Sci

Publication Date

09/1994

Volume

15

Pages

207 - 220

Keywords

Animals, Cell Division, Cyclosporine, Humans, Immunosuppressive Agents, Lymphocyte Activation, T-Lymphocytes, Tacrolimus, Thymus Gland