IL-2 and IL-15 manifest opposing effects on activation of nuclear factor of activated T cells.
IL-2 and IL-15 are cytokines involved in T cell activation and death. Their non-shared receptors, IL-2Ralpha and IL-15Ralpha, are important in the homeostasis of lymphocytes as evidenced by gene deletion studies. How these cytokine/receptor systems affect T cell antigen receptor signaling pathways is poorly understood. Here, we show that the IL-2 and IL-15 cytokine/receptor alpha systems regulate activation of nuclear factor of activated T cells (NF-AT) in opposing ways. IL-15Ralpha increased while IL-2Ralpha decreased basal NF-AT activation status in a Jurkat transient transfection model. The effect of each of the alpha chain receptors on NF-AT activation was further opposed by addition of the respective cytokine. These effects were inhibited by anti-cytokine and anti-cytokine receptor reagents as well as by inhibitors of TCR signaling. These results suggest a novel pathway of cytokine action to regulate T cell signaling, activation, death, and homeostasis.
Eicher
Donald M
DM
Division of Hematology-Oncology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Wearn Building, Room 448, Mailstop: WRN5061, 10900 Euclid Avenue, Cleveland, OH 44106-4937, USA. dme8@po.cwru.edu
D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; C508024:IL15RA protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D014157:Transcription Factors