Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression.
Here we demonstrate that CsA and DEX, at concentrations that markedly inhibited PHA-induced proliferation and IL 2 mRNA accumulation, partially diminished the expression of receptors for IL 2 on PBMC. This inhibition of IL 2 receptor expression occurred at a pretranslational level and involved a reduction in both high affinity and low affinity forms of the receptor. Although both CsA and DEX inhibited IL 2 receptor expression by about 50%, only CsA blocked the PHA-mediated induction of IL 2 responsivity in PBMC cultures. These data provide evidence that 1) CsA and DEX suppress the proliferation of T lymphocytes through distinct (though perhaps overlapping) mechanisms, 2) CsA (but not DEX) blocks the PHA-mediated induction of signals necessary for T cells to become capable of proliferating in response to IL 2, and 3) T cells regulate the expression of their genes for IL 2 and IL 2 receptors, at least in part, through independent mechanisms.
D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics; D003524:Cyclosporins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D010835:Phytohemagglutinins / Q000494:pharmacology; D011869:Radioligand Assay; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D003524:Cyclosporins; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D003907:Dexamethasone