0 10 Activation Activation NNP 11 13 of of IN 14 21 primary primary JJ 22 27 human human JJ 28 41 T-lymphocytes t-lymphocyte NNS 42 49 through through IN 50 53 CD2 cd2 NN 54 58 plus plus CC 59 63 CD28 cd28 NN 64 72 adhesion adhesion NN 73 82 molecules molecule NNS 83 90 induces induce VBZ 91 100 long-term long-term JJ 101 108 nuclear nuclear JJ 109 119 expression expression NN 120 122 of of IN 123 131 NF-kappa NF-kappa NNP 132 134 B. B. NNP 136 147 Stimulation stimulation NN 148 150 of of IN 151 157 highly highly RB 158 166 purified purify VBN 167 172 human human JJ 173 180 T-cells t-cell NNS 181 184 via via IN 185 188 CD2 cd2 NN 189 192 and and CC 193 197 CD28 cd28 NN 198 206 adhesion adhesion NN 207 216 molecules molecule NNS 217 224 induces induce VBZ 225 228 and and CC 229 238 maintains maintain VBZ 239 252 proliferation proliferation NN 253 256 for for IN 257 261 more more JJR 262 266 than than IN 267 268 3 3 CD 269 274 weeks week NNS 274 275 . . . 276 280 This this DT 281 287 potent potent JJ 288 299 interleukin interleukin NN 300 301 2 2 CD 302 303 ( ( ( 303 318 IL-2)-dependent il-2)-dependent JJ 319 329 activation activation NN 330 334 does do VBZ 335 338 not not RB 339 346 require require VB 347 356 monocytes monocyte NNS 357 359 or or CC 360 369 accessory accessory JJ 370 375 cells cell NNS 375 376 . . . 377 389 Long-lasting long-lasting JJ 390 394 IL-2 il-2 NN 395 406 receptivity receptivity NN 407 409 is be VBZ 410 420 associated associate VBN 421 425 with with IN 426 436 high-level high-level JJ 437 447 expression expression NN 448 450 of of IN 451 454 the the DT 455 464 inducible inducible JJ 465 469 IL-2 il-2 NN 470 478 receptor receptor NN 479 484 alpha alpha NN 485 490 chain chain NN 491 492 ( ( ( 492 497 IL-2R IL-2R NNP 498 503 alpha alpha NN 503 504 ) ) ) 505 509 gene gene NN 510 514 that that WDT 515 517 is be VBZ 518 527 regulated regulate VBN 528 530 at at IN 531 535 both both CC 536 551 transcriptional transcriptional JJ 552 555 and and CC 556 575 posttranscriptional posttranscriptional JJ 576 582 levels level NNS 582 583 . . . 584 592 Increase increase NN 593 595 of of IN 596 601 IL-2R IL-2R NNP 602 607 alpha alpha NN 608 612 gene gene NN 613 626 transcription transcription NN 627 635 involves involve VBZ 636 639 the the DT 640 648 enhanced enhance VBN 649 656 binding binding NN 657 659 of of IN 660 663 the the DT 664 677 transcription transcription NN 678 684 factor factor NN 685 693 NF-kappa NF-kappa NNP 694 695 B B NNP 696 698 to to TO 699 702 its its PRP$ 703 712 consensus consensus NN 713 721 sequence sequence NN 722 724 in in IN 725 728 the the DT 729 742 5’-regulatory 5'-regulatory JJ 743 749 region region NN 750 752 of of IN 753 756 the the DT 757 762 IL-2R IL-2R NNP 763 768 alpha alpha NN 769 773 gene gene NN 773 774 . . . 775 777 To to TO 778 785 dissect dissect VB 786 789 the the DT 790 799 molecular molecular JJ 800 805 basis basis NN 806 809 for for IN 810 813 the the DT 814 823 unusually unusually RB 824 834 persistent persistent JJ 835 848 transcription transcription NN 849 851 of of IN 852 855 the the DT 856 861 IL-2R IL-2R NNP 862 867 alpha alpha NN 868 872 gene gene NN 872 873 , , , 874 876 we we PRP 877 885 analyzed analyze VBD 886 893 nuclear nuclear JJ 894 902 NF-kappa NF-kappa NNP 903 904 B B NNP 905 912 binding bind VBG 913 915 to to TO 916 917 a a DT 918 930 radiolabeled radiolabele VBN 931 936 IL-2R il-2r NN 937 942 alpha alpha NN 943 948 kappa kappa NN 949 959 B-specific b-specific JJ 960 975 oligonucleotide oligonucleotide NN 976 981 probe probe NN 982 988 during during IN 989 992 the the DT 993 997 time time NN 998 1004 course course NN 1005 1007 of of IN 1008 1011 CD2 cd2 NN 1012 1013 + + CC 1014 1018 CD28 cd28 NN 1019 1029 activation activation NN 1029 1030 . . . 1031 1038 Resting rest VBG 1039 1045 T-cell T-cell NNP 1046 1053 nuclear nuclear JJ 1054 1062 extracts extract NNS 1063 1072 contained contain VBD 1073 1081 KBF1/p50 kbf1/p50 NN 1082 1091 homodimer homodimer NN 1091 1092 . . . 1093 1098 After after IN 1099 1110 stimulation stimulation NN 1110 1111 , , , 1112 1115 two two CD 1116 1119 new new JJ 1120 1125 kappa kappa NN 1126 1136 B-specific b-specific JJ 1137 1146 complexes complex NNS 1147 1151 were be VBD 1152 1162 identified identify VBN 1163 1165 as as IN 1166 1174 NF-kappa NF-kappa NNP 1175 1176 B B NNP 1177 1184 p50-p65 p50-p65 NN 1185 1196 heterodimer heterodimer NN 1197 1200 and and CC 1201 1209 putative putative JJ 1210 1215 c-Rel c-rel NN 1216 1225 homodimer homodimer NN 1226 1228 or or CC 1229 1238 c-Rel-p65 c-rel-p65 NN 1239 1250 heterodimer heterodimer NN 1250 1251 . . . 1252 1256 Both both DT 1257 1266 inducible inducible JJ 1267 1276 complexes complex NNS 1277 1286 persisted persist VBD 1287 1290 for for IN 1291 1293 at at IN 1294 1299 least least JJS 1300 1301 3 3 CD 1302 1307 weeks week NNS 1307 1308 . . . 1309 1314 Their their PRP$ 1315 1323 relative relative JJ 1324 1330 levels level NNS 1331 1335 were be VBD 1336 1340 very very RB 1341 1348 similar similar JJ 1349 1352 for for IN 1353 1356 the the DT 1357 1365 duration duration NN 1366 1368 of of IN 1369 1382 proliferation proliferation NN 1382 1383 . . . 1384 1386 In in IN 1387 1395 parallel parallel NN 1395 1396 , , , 1397 1400 CD2 cd2 NN 1401 1402 + + CC 1403 1407 CD28 cd28 NN 1408 1418 activation activation NN 1419 1428 triggered trigger VBD 1429 1430 a a DT 1431 1442 significant significant JJ 1443 1456 intracellular intracellular JJ 1457 1462 thiol thiol NN 1463 1471 decrease decrease NN 1471 1472 , , , 1473 1483 suggesting suggest VBG 1484 1488 that that IN 1489 1495 oxygen oxygen NN 1496 1504 radicals radical NNS 1505 1508 are be VBP 1509 1517 involved involve VBN 1518 1520 in in IN 1521 1524 the the DT 1525 1534 signaling signaling NN 1535 1542 pathway pathway NN 1543 1545 of of IN 1546 1554 adhesion adhesion NN 1555 1564 molecules molecule NNS 1564 1565 . . . 1566 1573 Finally finally RB 1573 1574 , , , 1575 1585 micromolar micromolar JJ 1586 1593 amounts amount NNS 1594 1596 of of IN 1597 1608 pyrrolidine pyrrolidine NN 1609 1624 dithiocarbamate dithiocarbamate NN 1624 1625 , , , 1626 1628 an an DT 1629 1635 oxygen oxygen NN 1636 1643 radical radical NN 1644 1653 scavenger scavenger NN 1654 1658 that that WDT 1659 1670 efficiently efficiently RB 1671 1678 blocked block VBD 1679 1682 the the DT 1683 1690 nuclear nuclear JJ 1691 1701 appearance appearance NN 1702 1704 of of IN 1705 1713 NF-kappa NF-kappa NNP 1714 1715 B B NNP 1716 1718 in in IN 1719 1732 T-lymphocytes T-lymphocyte NNP 1732 1733 , , , 1734 1738 also also RB 1739 1748 inhibited inhibit VBD 1749 1753 IL-2 il-2 NN 1754 1763 secretion secretion NN 1763 1764 , , , 1765 1770 IL-2R IL-2R NNP 1771 1776 alpha alpha NN 1777 1781 cell cell NN 1782 1789 surface surface NN 1790 1800 expression expression NN 1800 1801 , , , 1802 1805 and and CC 1806 1812 T-cell t-cell NN 1813 1826 proliferation proliferation NN 1826 1827 . . . 1828 1836 Together together RB 1836 1837 , , , 1838 1843 these these DT 1844 1851 results result NNS 1852 1859 suggest suggest VBP 1860 1864 that that IN 1865 1873 NF-kappa NF-kappa NNP 1874 1875 B B NNP 1876 1881 plays play VBZ 1882 1884 an an DT 1885 1894 important important JJ 1895 1899 role role NN 1900 1902 in in IN 1903 1912 long-term long-term JJ 1913 1923 activation activation NN 1924 1926 of of IN 1927 1932 human human JJ 1933 1940 primary primary JJ 1941 1954 T-lymphocytes t-lymphocyte NNS 1955 1958 via via IN 1959 1962 CD2 cd2 NN 1963 1964 + + CC 1965 1969 CD28 cd28 NN 1969 1970 . . .