0 2 In in FW 3 7 vivo vivo FW 8 17 anergized anergize VBN 18 22 CD4+ cd4+ JJ 23 24 T t NN 25 30 cells cell NNS 31 38 express express VBP 39 48 perturbed perturb VBN 49 53 AP-1 ap-1 NN 54 57 and and CC 58 66 NF-kappa NF-kappa NNP 67 68 B B NNP 69 82 transcription transcription NN 83 90 factors factor NNS 90 91 . . . 93 99 Anergy Anergy NNP 100 102 is be VBZ 103 104 a a DT 105 110 major major JJ 111 120 mechanism mechanism NN 121 123 to to TO 124 130 ensure ensure VB 131 147 antigen-specific antigen-specific JJ 148 157 tolerance tolerance NN 158 160 in in IN 161 162 T t NN 163 174 lymphocytes lymphocyte NNS 175 177 in in IN 178 181 the the DT 182 187 adult adult NN 187 188 . . . 189 191 In in FW 192 196 vivo vivo FW 196 197 , , , 198 204 anergy anergy NN 205 208 has have VBZ 209 215 mainly mainly RB 216 220 been be VBN 221 228 studied study VBN 229 231 at at IN 232 235 the the DT 236 244 cellular cellular JJ 245 250 level level NN 250 251 . . . 252 254 In in IN 255 259 this this DT 260 265 study study NN 265 266 , , , 267 269 we we PRP 270 274 used use VBD 275 278 the the DT 279 296 T-cell-activating t-cell-activating JJ 297 309 superantigen superantigen NN 310 324 staphylococcal staphylococcal JJ 325 336 enterotoxin enterotoxin NN 337 338 A A NNP 339 340 ( ( ( 340 343 SEA SEA NNP 343 344 ) ) ) 345 347 to to TO 348 359 investigate investigate VB 360 369 molecular molecular JJ 370 380 mechanisms mechanism NNS 381 383 of of IN 384 396 T-lymphocyte T-lymphocyte NNP 397 403 anergy anergy NN 404 406 in in FW 407 411 vivo vivo FW 411 412 . . . 413 422 Injection injection NN 423 425 of of IN 426 429 SEA SEA NNP 430 432 to to TO 433 438 adult adult JJ 439 443 mice mouse NNS 444 453 activates activate VBZ 454 458 CD4+ cd4+ JJ 459 460 T t NN 461 466 cells cell NNS 467 477 expressing express VBG 478 485 certain certain JJ 486 492 T-cell t-cell NN 493 501 receptor receptor NN 502 503 ( ( ( 503 506 TCR TCR NNP 506 507 ) ) ) 508 516 variable variable JJ 517 523 region region NN 524 534 beta-chain beta-chain NN 535 543 families family NNS 544 547 and and CC 548 555 induces induce VBZ 556 562 strong strong JJ 563 566 and and CC 567 572 rapid rapid JJ 573 583 production production NN 584 586 of of IN 587 598 interleukin interleukin NN 599 600 2 2 CD 601 602 ( ( ( 602 606 IL-2 il-2 NN 606 607 ) ) ) 607 608 . . . 609 611 In in IN 612 620 contrast contrast NN 620 621 , , , 622 630 repeated repeat VBN 631 641 injections injection NNS 642 644 of of IN 645 648 SEA SEA NNP 649 654 cause cause VBP 655 659 CD4+ cd4+ JJ 660 666 T-cell t-cell NN 667 675 deletion deletion NN 676 679 and and CC 680 686 anergy anergy NN 687 689 in in IN 690 693 the the DT 694 703 remaining remain VBG 704 708 CD4+ cd4+ JJ 709 710 T t NN 711 716 cells cell NNS 716 717 , , , 718 731 characterized characterize VBN 732 734 by by IN 735 742 reduced reduce VBN 743 753 expression expression NN 754 756 of of IN 757 761 IL-2 il-2 NN 762 764 at at IN 765 769 mRNA mRNA NNP 770 773 and and CC 774 781 protein protein NN 782 788 levels level NNS 788 789 . . . 790 792 We we PRP 793 801 analyzed analyze VBD 802 812 expression expression NN 813 815 of of IN 816 820 AP-1 ap-1 NN 820 821 , , , 822 830 NF-kappa NF-kappa NNP 831 832 B B NNP 832 833 , , , 834 839 NF-AT NF-AT NNP 839 840 , , , 841 844 and and CC 845 852 octamer octamer NN 853 860 binding binding NN 861 874 transcription transcription NN 875 882 factors factor NNS 882 883 , , , 884 889 which which WDT 890 893 are be VBP 894 899 known know VBN 900 902 to to TO 903 905 be be VB 906 914 involved involve VBN 915 917 in in IN 918 921 the the DT 922 932 regulation regulation NN 933 935 of of IN 936 940 IL-2 il-2 NN 941 945 gene gene NN 946 954 promoter promoter NN 955 963 activity activity NN 963 964 . . . 965 970 Large large JJ 971 978 amounts amount NNS 979 981 of of IN 982 986 AP-1 AP-1 NNP 987 990 and and CC 991 999 NF-kappa NF-kappa NNP 1000 1001 B B NNP 1002 1005 and and CC 1006 1017 significant significant JJ 1018 1028 quantities quantity NNS 1029 1031 of of IN 1032 1037 NF-AT NF-AT NNP 1038 1042 were be VBD 1043 1050 induced induce VBN 1051 1053 in in IN 1054 1067 SEA-activated sea-activated JJ 1068 1072 CD4+ cd4+ JJ 1073 1079 spleen spleen NN 1080 1081 T t NN 1082 1087 cells cell NNS 1087 1088 , , , 1089 1096 whereas whereas IN 1097 1102 Oct-1 oct-1 NN 1103 1106 and and CC 1107 1112 Oct-2 oct-2 NN 1113 1116 DNA dna NN 1117 1124 binding binding NN 1125 1133 activity activity NN 1134 1137 was be VBD 1138 1145 similar similar JJ 1146 1148 in in IN 1149 1153 both both CC 1154 1161 resting rest VBG 1162 1165 and and CC 1166 1175 activated activate VBN 1176 1177 T t NN 1178 1183 cells cell NNS 1183 1184 . . . 1185 1187 In in IN 1188 1196 contrast contrast NN 1196 1197 , , , 1198 1205 anergic anergic JJ 1206 1210 CD4+ cd4+ JJ 1211 1212 T t NN 1213 1218 cells cell NNS 1219 1228 contained contain VBD 1229 1237 severely severely RB 1238 1245 reduced reduce VBN 1246 1252 levels level NNS 1253 1255 of of IN 1256 1260 AP-1 ap-1 NN 1261 1264 and and CC 1265 1283 Fos/Jun-containing fos/jun-containing JJ 1284 1289 NF-AT NF-AT NNP 1290 1299 complexes complex NNS 1300 1303 but but CC 1304 1313 expressed express VBD 1314 1325 significant significant JJ 1326 1333 amounts amount NNS 1334 1336 of of IN 1337 1345 NF-kappa NF-kappa NNP 1346 1347 B B NNP 1348 1351 and and CC 1352 1355 Oct Oct NNP 1356 1363 binding binding NN 1364 1372 proteins protein NNS 1373 1378 after after IN 1379 1382 SEA SEA NNP 1383 1394 stimulation stimulation NN 1394 1395 . . . 1396 1406 Resolution Resolution NNP 1407 1409 of of IN 1410 1413 the the DT 1414 1422 NF-kappa NF-kappa NNP 1423 1424 B B NNP 1425 1432 complex complex NN 1433 1445 demonstrated demonstrate VBD 1446 1457 predominant predominant JJ 1458 1468 expression expression NN 1469 1471 of of IN 1472 1479 p50-p65 p50-p65 NN 1480 1492 heterodimers heterodimer NNS 1493 1495 in in IN 1496 1505 activated activate VBN 1506 1510 CD4+ cd4+ JJ 1511 1512 T t NN 1513 1518 cells cell NNS 1518 1519 , , , 1520 1525 while while IN 1526 1533 anergic anergic JJ 1534 1539 cells cell NNS 1540 1546 mainly mainly RB 1547 1556 expressed express VBD 1557 1560 the the DT 1561 1578 transcriptionally transcriptionally RB 1579 1587 inactive inactive JJ 1588 1591 p50 p50 NN 1592 1601 homodimer homodimer NN 1601 1602 . . . 1603 1608 These these DT 1609 1620 alterations alteration NNS 1621 1623 of of IN 1624 1637 transcription transcription NN 1638 1645 factors factor NNS 1646 1649 are be VBP 1650 1656 likely likely JJ 1657 1659 to to TO 1660 1662 be be VB 1663 1674 responsible responsible JJ 1675 1678 for for IN 1679 1689 repression repression NN 1690 1692 of of IN 1693 1697 IL-2 il-2 NN 1698 1700 in in IN 1701 1708 anergic anergic JJ 1709 1710 T t NN 1711 1716 cells cell NNS 1716 1717 . . .