Distribution of IL-15 receptor alpha-chains on human peripheral blood mononuclear cells and effect of immunosuppressive drugs on receptor expression.
IL-15, a newly described cytokine exerting IL-2-like in vitro activities, binds to and induces proliferation of cells co-expressing IL-15R alpha, IL-2R beta, and IL-2R gamma chains. To study the expression of human IL-15R alpha chains, we have utilized tagged human IL-15 protein and FACS analysis. In contrast to resting cells, mitogen-activated macrophages, NK cells, and CD4+ and CD8+ T cells express IL-15R alpha chains. Neither IL-2R alpha nor IL-2R beta chains are required for IL-15 binding. Dexamethasone, but not cyclosporine or rapamycin, blocks mitogen-induced IL-15R alpha expression. Dexamethasone-pretreated cells respond to IL-15 poorly, while the response to IL-2 is not affected. Thus, despite structural and functional similarities between IL-2R alpha and IL-15R alpha chains, the activation-triggered mechanisms of induction are different. Since IL-15R alpha chain is necessary and sufficient for IL-15 binding, regulation of IL-15R alpha expression may represent a new target for T cell-directed pharmacologic intervention.
Chae
D W
DW
Harvard Medical School, Department of Medicine, Beth Israel Hospital, Boston, MA 02215, USA.
Nosaka
Y
Y
Strom
T B
TB
Maslinski
W
W
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D020123:Sirolimus; D013601:T-Lymphocytes / Q000737:chemistry* / Q000648:ultrastructure
C508024:IL15RA protein, human; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011090:Polyenes; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D018664:Interleukin-12; D003907:Dexamethasone; D016572:Cyclosporine; D020123:Sirolimus