Journal Article10.1126/SCIENCE.6238408
Cyclophilin: A Specific Cytosolic Binding Protein for Cyclosporin A
TL;DR: Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.
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Abstract: Cyclophilin, a specific cytosolic binding protein responsible for the concentration of the immunosuppressant cyclosporin A by lymphoid cells, was purified to homogeneity from bovine thymocytes. Cation-exchange high-performance liquid chromatography resolved a major and minor cyclophilin species that bind cyclosporin A with a dissociation constant of about 2 X 10(-7) moles per liter and specific activities of 77 and 67 micrograms per milligram of protein, respectively. Both cyclophilin species have an apparent molecular weight of 15,000, an isoelectric point of 9.6, and nearly identical amino acid compositions. A portion of the NH2-terminal amino acid sequence of the major species was determined. The cyclosporin A-binding activity of cyclophilin is sulfhydryl dependent, unstable at 56 degrees C and at pH 4 or 9.5, and sensitive to trypsin but not to chymotrypsin digestion. Cyclophilin specifically binds a series of cyclosporin analogs in proportion to their activity in a mixed lymphocyte reaction. Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.
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Cyclosporin A blocks receptors for HLA-DR antigens on T cells
Ronald Palacios,Göran Möller +1 more
TL;DR: Results suggested that the HLA-DR antigens rendered resting T cells sensitive to IL-2 and participated actively in the production of the growth factor in the autologous mixed lymphocyte reaction.
Cyclosporine: Five Years' Experience in Cadaveric Renal Transplantation
TL;DR: Serum creatinine levels have been higher in cyclosporine-treated patients with functioning grafts, but graft deterioration has not occurred after more than three years, and the rates of patient and graft survival remain superior to those with conventional immunosuppression.
Activation of antigen-specific suppressor T cells in the presence of cyclosporin requires interactions between T cells of inducer and suppressor lineage.
TL;DR: Mixed leukocyte reactions in the presence of cyclosporin, a fungal metabolite which prevents the generation of cytotoxic lymphocytes while permitting activation of suppressor cells, results from an ordered series of interactions between T cells of distinct phenotype.