0 7 Nuclear nuclear JJ 8 18 appearance appearance NN 19 21 of of IN 22 23 a a DT 24 30 factor factor NN 31 35 that that WDT 36 41 binds bind VBZ 42 45 the the DT 46 50 CD28 cd28 NN 51 59 response response NN 60 67 element element NN 68 74 within within IN 75 78 the the DT 79 92 interleukin-2 interleukin-2 NN 93 101 enhancer enhancer NN 102 112 correlates correlate VBZ 113 117 with with IN 118 131 interleukin-2 interleukin-2 NN 132 142 production production NN 142 143 . . . 145 155 Activation Activation NNP 156 158 of of IN 159 160 T t NN 161 172 lymphocytes lymphocyte NNS 173 181 requires require VBZ 182 185 the the DT 186 194 combined combined JJ 195 204 signaling signaling NN 205 207 of of IN 208 211 the the DT 212 213 T t NN 214 218 cell cell NN 219 227 receptor receptor NN 228 231 and and CC 232 245 costimulatory costimulatory JJ 246 255 molecules molecule NNS 256 260 such such JJ 261 263 as as IN 264 268 CD28 cd28 NN 268 269 . . . 270 273 The the DT 274 281 ability ability NN 282 284 of of IN 285 286 T t NN 287 292 cells cell NNS 293 295 to to TO 296 303 produce produce VB 304 317 interleukin-2 interleukin-2 NN 318 319 ( ( ( 319 323 IL-2 il-2 NN 323 324 ) ) ) 325 327 is be VBZ 328 329 a a DT 330 338 critical critical JJ 339 346 control control NN 347 352 point point NN 353 355 in in IN 356 357 T t NN 358 368 lymphocyte lymphocyte NN 369 379 activation activation NN 379 380 . . . 381 384 The the DT 385 389 IL-2 il-2 NN 390 398 enhancer enhancer NN 399 407 contains contain VBZ 408 409 a a DT 410 420 functional functional JJ 421 426 motif motif NN 427 432 named name VBN 433 437 CD28 cd28 NN 438 446 response response NN 447 454 element element NN 455 456 ( ( ( 456 462 CD28RE CD28RE NNP 462 463 ) ) ) 464 468 that that WDT 469 475 serves serve VBZ 476 477 a a DT 478 482 role role NN 483 485 as as IN 486 487 a a DT 488 494 target target NN 495 498 for for IN 499 508 mitogenic mitogenic JJ 509 510 T t NN 511 515 cell cell NN 516 526 activation activation NN 527 534 signals signal NNS 534 535 . . . 536 539 The the DT 540 546 CD28RE CD28RE NNP 547 555 sequence sequence NN 556 563 reveals reveal VBZ 564 574 similarity similarity NN 575 577 to to TO 578 581 the the DT 582 591 consensus consensus NN 592 598 kappaB kappab NN 599 606 binding binding NN 607 612 motif motif NN 612 613 . . . 614 618 Here here RB 619 621 we we PRP 622 633 demonstrate demonstrate VBP 634 638 that that IN 639 645 CD28RE CD28RE NNP 646 651 binds bind VBZ 652 654 an an DT 655 664 inducible inducible JJ 665 672 protein protein NN 673 677 with with IN 678 679 a a DT 680 689 molecular molecular JJ 690 694 mass mass NN 695 697 of of IN 698 711 approximately approximately RB 712 714 35 35 CD 715 718 kDa kda NN 719 725 called call VBN 726 733 nuclear nuclear JJ 734 740 factor factor NN 741 743 of of IN 744 763 mitogenic-activated mitogenic-activated JJ 764 765 T t NN 766 771 cells cell NNS 772 773 ( ( ( 773 782 NF-MATp35 NF-MATp35 NNP 782 783 ) ) ) 784 788 that that WDT 789 791 is be VBZ 792 799 clearly clearly RB 800 809 different different JJ 810 814 from from IN 815 818 the the DT 819 824 known know VBN 825 828 NF- nf- NF- 829 839 kappaB/Rel kappab/rel NN 840 846 family family NN 847 854 members member NNS 854 855 . . . 856 865 Induction Induction NNP 866 868 of of IN 869 878 NF-MATp35 NF-MATp35 NNP 879 882 was be VBD 883 888 shown show VBN 889 891 to to TO 892 898 depend depend VB 899 901 on on IN 902 904 de de FW 905 909 novo novo FW 910 917 protein protein NN 918 927 synthesis synthesis NN 928 931 and and CC 932 935 was be VBD 936 946 restricted restricted JJ 947 949 to to TO 950 951 T t NN 952 957 cells cell NNS 958 962 that that WDT 963 971 received receive VBD 972 973 a a DT 974 983 mitogenic mitogenic JJ 984 995 combination combination NN 996 998 of of IN 999 1000 T t NN 1001 1005 cell cell NN 1006 1013 stimuli stimulus NNS 1013 1014 , , , 1015 1018 not not RB 1019 1030 necessarily necessarily RB 1031 1040 including include VBG 1041 1045 CD28 cd28 NN 1046 1055 signaling signaling NN 1055 1056 . . . 1057 1069 Nonmitogenic nonmitogenic JJ 1070 1071 T t NN 1072 1076 cell cell NN 1077 1088 stimulation stimulation NN 1089 1092 did do VBD 1093 1096 not not RB 1097 1103 result result VB 1104 1106 in in IN 1107 1117 appearance appearance NN 1118 1120 of of IN 1121 1130 NF-MATp35 NF-MATp35 NNP 1130 1131 . . . 1132 1137 These these DT 1138 1145 results result NNS 1146 1154 indicate indicate VBP 1155 1159 that that IN 1160 1169 mitogenic mitogenic JJ 1170 1182 combinations combination NNS 1183 1185 of of IN 1186 1187 T t NN 1188 1192 cell cell NN 1193 1203 activation activation NN 1204 1211 signals signal NNS 1212 1215 are be VBP 1216 1226 integrated integrate VBN 1227 1229 at at IN 1230 1233 the the DT 1234 1239 level level NN 1240 1242 of of IN 1243 1252 NF-MATp35 nf-matp35 NN 1253 1262 induction induction NN 1262 1263 . . . 1264 1271 Similar similar JJ 1272 1274 to to TO 1275 1278 its its PRP$ 1279 1285 effect effect NN 1286 1288 on on IN 1289 1293 IL-2 il-2 NN 1294 1304 production production NN 1304 1305 , , , 1306 1317 cyclosporin cyclosporin NN 1318 1319 A a NN 1320 1329 inhibited inhibit VBD 1330 1333 the the DT 1334 1343 induction induction NN 1344 1346 of of IN 1347 1356 NF-MATp35 NF-MATp35 NNP 1356 1357 . . . 1358 1363 Taken take VBN 1364 1372 together together RB 1372 1373 , , , 1374 1379 these these DT 1380 1384 data datum NNS 1385 1396 demonstrate demonstrate VBP 1397 1401 that that IN 1402 1405 the the DT 1406 1413 nuclear nuclear JJ 1414 1424 appearance appearance NN 1425 1427 of of IN 1428 1437 NF-MATp35 NF-MATp35 NNP 1438 1443 shows show VBZ 1444 1453 excellent excellent JJ 1454 1465 correlation correlation NN 1466 1470 with with IN 1471 1475 IL-2 il-2 NN 1476 1486 production production NN 1486 1487 , , , 1488 1493 which which WDT 1494 1496 is be VBZ 1497 1498 a a DT 1499 1505 unique unique JJ 1506 1520 characteristic characteristic NN 1521 1526 among among IN 1527 1534 nuclear nuclear JJ 1535 1542 factors factor NNS 1543 1553 implicated implicate VBN 1554 1556 in in IN 1557 1560 the the DT 1561 1568 control control NN 1569 1571 of of IN 1572 1576 IL-2 il-2 NN 1577 1581 gene gene NN 1582 1592 expression expression NN 1592 1593 . . .