0 16 Interferon-alpha Interferon-alpha NNP 17 26 activates activate VBZ 27 35 multiple multiple JJ 36 40 STAT stat NN 41 49 proteins protein NNS 50 53 and and CC 54 65 upregulates upregulate VBZ 66 90 proliferation-associated proliferation-associated JJ 91 101 IL-2Ralpha IL-2Ralpha NNP 101 102 , , , 103 108 c-myc c-myc NN 108 109 , , , 110 113 and and CC 114 119 pim-1 pim-1 NN 120 125 genes gene NNS 126 128 in in IN 129 134 human human JJ 135 136 T t NN 137 142 cells cell NNS 142 143 . . . 145 161 Interferon-alpha Interferon-alpha NNP 162 163 ( ( ( 163 172 IFN-alpha IFN-alpha NNP 172 173 ) ) ) 174 176 is be VBZ 177 178 a a DT 179 190 pleiotropic pleiotropic JJ 191 199 cytokine cytokine NN 200 204 that that WDT 205 208 has have VBZ 209 218 antiviral antiviral JJ 218 219 , , , 220 237 antiproliferative antiproliferative JJ 237 238 , , , 239 242 and and CC 243 259 immunoregulatory immunoregulatory JJ 260 269 functions function NNS 269 270 . . . 271 276 There there EX 277 279 is be VBZ 280 290 increasing increase VBG 291 299 evidence evidence NN 300 304 that that IN 305 314 IFN-alpha IFN-alpha NNP 315 318 has have VBZ 319 321 an an DT 322 331 important important JJ 332 336 role role NN 337 339 in in IN 340 346 T-cell t-cell NN 347 354 biology biology NN 354 355 . . . 356 358 We we PRP 359 363 have have VBP 364 372 analyzed analyze VBN 373 376 the the DT 377 387 expression expression NN 388 390 of of IN 391 401 IL-2Ralpha IL-2Ralpha NNP 401 402 , , , 403 408 c-myc c-myc NN 408 409 , , , 410 413 and and CC 414 419 pim-1 pim-1 NN 420 425 genes gene NNS 426 428 in in IN 429 447 anti-CD3-activated anti-cd3-activated JJ 448 453 human human JJ 454 455 T t NN 456 467 lymphocytes lymphocyte NNS 467 468 . . . 469 472 The the DT 473 482 induction induction NN 483 485 of of IN 486 491 these these DT 492 497 genes gene NNS 498 500 is be VBZ 501 511 associated associate VBN 512 516 with with IN 517 530 interleukin-2 interleukin-2 NN 531 532 ( ( ( 532 545 IL-2)-induced il-2)-induced JJ 546 552 T-cell T-cell NNP 553 566 proliferation proliferation NN 566 567 . . . 568 577 Treatment Treatment NNP 578 580 of of IN 581 582 T t NN 583 594 lymphocytes lymphocyte NNS 595 599 with with IN 600 609 IFN-alpha IFN-alpha NNP 609 610 , , , 611 615 IL-2 IL-2 NNP 615 616 , , , 617 622 IL-12 il-12 NN 622 623 , , , 624 627 and and CC 628 633 IL-15 IL-15 NNP 634 645 upregulated upregulate VBD 646 656 IL-2Ralpha IL-2Ralpha NNP 656 657 , , , 658 663 c-myc c-myc NN 663 664 , , , 665 668 and and CC 669 674 pim-1 pim-1 NN 675 679 gene gene NN 680 690 expression expression NN 690 691 . . . 692 701 IFN-alpha IFN-alpha NNP 702 706 also also RB 707 717 sensitized sensitize VBD 718 719 T t NN 720 725 cells cell NNS 726 728 to to TO 729 741 IL-2-induced il-2-induced JJ 742 755 proliferation proliferation NN 755 756 , , , 757 764 further further RB 765 775 suggesting suggest VBG 776 780 that that IN 781 790 IFN-alpha IFN-alpha NNP 791 794 may may MD 795 797 be be VB 798 806 involved involve VBN 807 809 in in IN 810 813 the the DT 814 824 regulation regulation NN 825 827 of of IN 828 834 T-cell t-cell NN 835 846 mitogenesis mitogenesis NN 846 847 . . . 848 852 When when WRB 853 855 we we PRP 856 864 analyzed analyze VBD 865 868 the the DT 869 875 nature nature NN 876 878 of of IN 879 883 STAT STAT NNP 884 892 proteins protein NNS 893 900 capable capable JJ 901 903 of of IN 904 911 binding bind VBG 912 914 to to TO 915 925 IL-2Ralpha IL-2Ralpha NNP 925 926 , , , 927 932 pim-1 pim-1 NN 932 933 , , , 934 937 and and CC 938 943 IRF-1 IRF-1 NNP 944 947 GAS GAS NNP 948 956 elements element NNS 957 962 after after IN 963 971 cytokine cytokine NN 972 983 stimulation stimulation NN 983 984 , , , 985 987 we we PRP 988 996 observed observe VBD 997 1014 IFN-alpha-induced ifn-alpha-induced JJ 1015 1022 binding binding NN 1023 1025 of of IN 1026 1031 STAT1 STAT1 NNP 1031 1032 , , , 1033 1038 STAT3 STAT3 NNP 1038 1039 , , , 1040 1043 and and CC 1044 1049 STAT4 stat4 NN 1049 1050 , , , 1051 1054 but but CC 1055 1058 not not RB 1059 1064 STAT5 stat5 NN 1065 1067 to to TO 1068 1071 all all DT 1072 1074 of of IN 1075 1080 these these DT 1081 1089 elements element NNS 1089 1090 . . . 1091 1094 Yet yet RB 1094 1095 , , , 1096 1105 IFN-alpha IFN-alpha NNP 1106 1109 was be VBD 1110 1114 able able JJ 1115 1117 to to TO 1118 1126 activate activate VB 1127 1134 binding binding NN 1135 1137 of of IN 1138 1143 STAT5 stat5 NN 1144 1146 to to TO 1147 1150 the the DT 1151 1164 high-affinity high-affinity JJ 1165 1170 IFP53 IFP53 NNP 1171 1174 GAS GAS NNP 1175 1179 site site NN 1179 1180 . . . 1181 1190 IFN-alpha IFN-alpha NNP 1191 1199 enhanced enhance VBD 1200 1208 tyrosine tyrosine NN 1209 1224 phosphorylation phosphorylation NN 1225 1227 of of IN 1228 1233 STAT1 STAT1 NNP 1233 1234 , , , 1235 1240 STAT3 STAT3 NNP 1240 1241 , , , 1242 1247 STAT4 STAT4 NNP 1247 1248 , , , 1249 1255 STAT5a STAT5a NNP 1255 1256 , , , 1257 1260 and and CC 1261 1268 STAT5b. STAT5b. NNP 1269 1274 IL-12 il-12 NN 1275 1282 induced induce VBD 1283 1288 STAT4 stat4 NN 1289 1292 and and CC 1293 1297 IL-2 IL-2 NNP 1298 1301 and and CC 1302 1307 IL-15 IL-15 NNP 1308 1315 induced induce VBD 1316 1321 STAT5 stat5 NN 1322 1329 binding binding NN 1330 1332 to to TO 1333 1336 the the DT 1337 1340 GAS GAS NNP 1341 1349 elements element NNS 1349 1350 . . . 1351 1356 Taken take VBN 1357 1365 together together RB 1365 1366 , , , 1367 1370 our our PRP$ 1371 1378 results result NNS 1379 1386 suggest suggest VBP 1387 1391 that that IN 1392 1401 IFN-alpha IFN-alpha NNP 1401 1402 , , , 1403 1407 IL-2 IL-2 NNP 1407 1408 , , , 1409 1414 IL-12 il-12 NN 1414 1415 , , , 1416 1419 and and CC 1420 1425 IL-15 IL-15 NNP 1426 1430 have have VBP 1431 1442 overlapping overlap VBG 1443 1453 activities activity NNS 1454 1456 on on IN 1457 1462 human human JJ 1463 1464 T t NN 1465 1470 cells cell NNS 1470 1471 . . . 1472 1477 These these DT 1478 1486 findings finding NNS 1487 1491 thus thus RB 1492 1501 emphasize emphasize VBP 1502 1505 the the DT 1506 1516 importance importance NN 1517 1519 of of IN 1520 1529 IFN-alpha IFN-alpha NNP 1530 1532 as as IN 1533 1534 a a DT 1535 1541 T-cell t-cell NN 1542 1552 regulatory regulatory JJ 1553 1561 cytokine cytokine NN 1561 1562 . . .