0 7 Nuclear nuclear JJ 8 14 factor factor NN 15 17 of of IN 18 27 activated activate VBN 28 29 T t NN 30 35 cells cell NNS 36 39 and and CC 40 44 AP-1 ap-1 NN 45 48 are be VBP 49 61 insufficient insufficient JJ 62 65 for for IN 66 70 IL-2 il-2 NN 71 79 promoter promoter NN 80 90 activation activation NN 90 91 : : : 92 103 requirement requirement NN 104 107 for for IN 108 112 CD28 cd28 NN 113 126 up-regulation up-regulation NN 127 129 of of IN 130 135 RE/AP RE/AP NNP 135 136 . . . 138 142 IL-2 il-2 NN 143 147 gene gene NN 148 161 transcription transcription NN 162 164 in in IN 165 166 T t NN 167 172 cells cell NNS 173 181 requires require VBZ 182 186 both both CC 187 190 TCR TCR NNP 191 194 and and CC 195 208 costimulatory costimulatory JJ 209 216 signals signal NNS 216 217 . . . 218 222 IL-2 il-2 NN 223 231 promoter promoter NN 232 242 activation activation NN 243 245 in in IN 246 252 Jurkat Jurkat NNP 253 254 T t NN 255 260 cells cell NNS 261 271 stimulated stimulate VBN 272 276 with with IN 277 289 superantigen superantigen NN 290 299 presented present VBN 300 302 by by IN 303 307 Raji Raji NNP 308 309 B B NNP 310 315 cells cell NNS 316 324 requires require VBZ 325 329 CD28 cd28 NN 330 340 activation activation NN 340 341 . . . 342 345 The the DT 346 354 addition addition NN 355 357 of of IN 358 366 rCTLA4Ig rctla4ig NN 366 367 , , , 368 373 which which WDT 374 380 blocks block VBZ 381 385 CD28 cd28 NN 386 393 binding binding NN 394 396 to to TO 397 400 its its PRP$ 401 407 ligand ligand NN 407 408 , , , 409 411 to to TO 412 415 the the DT 416 424 cultures culture NNS 425 434 decreased decrease VBD 435 439 IL-2 il-2 NN 440 448 promoter promoter NN 449 459 activation activation NN 460 462 by by IN 463 466 >80 >80 CD 466 467 % % NN 467 468 . . . 469 482 Interestingly interestingly RB 482 483 , , , 484 491 CTLA4Ig CTLA4Ig NNP 492 495 did do VBD 496 499 not not RB 500 513 significantly significantly RB 514 521 inhibit inhibit VB 522 525 the the DT 526 536 activation activation NN 537 539 of of IN 540 546 either either CC 547 549 NF nf NN 550 552 of of IN 553 562 activated activate VBN 563 564 T t NN 565 570 cells cell NNS 571 572 ( ( ( 572 576 NFAT NFAT NNP 576 577 ) ) ) 578 580 or or CC 581 585 AP-1 ap-1 NN 586 595 reporters reporter NNS 595 596 . . . 597 606 Therefore therefore RB 606 607 , , , 608 618 activation activation NN 619 621 of of IN 622 626 NFAT NFAT NNP 627 630 and and CC 631 635 AP-1 ap-1 NN 636 638 is be VBZ 639 651 insufficient insufficient JJ 652 655 for for IN 656 660 IL-2 il-2 NN 661 669 promoter promoter NN 670 680 activation activation NN 680 681 . . . 682 684 In in IN 685 693 contrast contrast NN 693 694 , , , 695 697 an an DT 698 703 RE/AP RE/AP NNP 704 712 reporter reporter NN 713 716 was be VBD 717 724 blocked block VBN 725 727 by by IN 728 735 CTLA4Ig ctla4ig NN 736 738 by by IN 739 742 >90 >90 CD 742 743 % % NN 743 744 . . . 745 749 Thus thus RB 749 750 , , , 751 754 the the DT 755 766 requirement requirement NN 767 770 for for IN 771 775 CD28 cd28 NN 776 778 in in IN 779 783 IL-2 il-2 NN 784 792 promoter promoter NN 793 803 activation activation NN 804 811 appears appear VBZ 812 814 to to TO 815 817 be be VB 818 821 due due IN 822 824 to to TO 825 830 RE/AP RE/AP NNP 831 834 and and CC 835 838 not not RB 839 842 the the DT 843 847 NFAT nfat NN 848 850 or or CC 851 855 AP-1 ap-1 NN 856 861 sites site NNS 861 862 . . . 863 865 In in IN 866 874 addition addition NN 874 875 , , , 876 881 these these DT 882 886 data datum NNS 887 894 suggest suggest VBP 895 899 that that IN 900 915 transcriptional transcriptional JJ 916 926 activation activation NN 927 929 of of IN 930 935 RE/AP RE/AP NNP 936 938 is be VBZ 939 942 not not RB 943 951 mediated mediate VBN 952 954 by by IN 955 959 NFAT NFAT NNP 959 960 , , , 961 968 because because IN 969 979 activation activation NN 980 982 of of IN 983 984 a a DT 985 989 NFAT NFAT NNP 990 998 reporter reporter NN 999 1001 is be VBZ 1002 1005 not not RB 1006 1014 affected affect VBN 1015 1017 by by IN 1018 1021 the the DT 1022 1030 addition addition NN 1031 1033 of of IN 1034 1041 CTLA4Ig CTLA4Ig NNP 1041 1042 . . .