0 10 Inhibition Inhibition NNP 11 13 of of IN 14 24 activation activation NN 25 27 of of IN 28 41 transcription transcription NN 42 48 factor factor NN 49 53 AP-1 ap-1 NN 54 56 by by IN 57 61 CD28 cd28 NN 62 72 signalling signalling NN 73 75 in in IN 76 81 human human JJ 82 89 T-cells t-cell NNS 89 90 . . . 92 106 Co-stimulation co-stimulation NN 107 109 of of IN 110 123 T-lymphocytes t-lymphocyte NNS 124 126 by by IN 127 133 T-cell t-cell NN 134 142 receptor receptor NN 143 144 ( ( ( 144 147 TcR TcR NNP 147 148 ) ) ) 149 158 occupancy occupancy NN 159 162 and and CC 163 173 activation activation NN 174 176 of of IN 177 180 the the DT 181 185 CD28 cd28 NN 186 193 surface surface NN 194 202 molecule molecule NN 203 210 results result VBZ 211 213 in in IN 214 222 enhanced enhance VBN 223 236 proliferation proliferation NN 237 240 and and CC 241 252 interleukin interleukin NN 253 254 2 2 CD 255 256 ( ( ( 256 260 IL-2 il-2 NN 260 261 ) ) ) 262 272 production production NN 272 273 . . . 274 277 The the DT 278 286 increase increase NN 287 289 in in IN 290 294 IL-2 il-2 NN 295 299 gene gene NN 300 310 expression expression NN 311 320 triggered trigger VBN 321 323 by by IN 324 328 CD28 cd28 NN 329 337 involves involve VBZ 338 339 a a DT 340 345 kappa kappa NN 346 352 B-like b-like JJ 353 361 sequence sequence NN 362 364 in in IN 365 368 the the DT 369 382 5’-regulatory 5'-regulatory JJ 383 389 region region NN 390 392 of of IN 393 396 the the DT 397 401 IL-2 il-2 NN 402 410 promoter promoter NN 410 411 , , , 412 418 called call VBN 419 434 CD28-responsive cd28-responsive JJ 435 442 element element NN 442 443 . . . 444 455 Stimulation stimulation NN 456 458 of of IN 459 466 T-cells t-cell NNS 467 469 by by IN 470 479 agonistic agonistic JJ 480 489 anti-CD28 anti-cd28 JJ 490 500 antibodies antibody NNS 501 503 in in IN 504 515 conjunction conjunction NN 516 520 with with IN 521 528 phorbol phorbol NN 529 541 12-myristate 12-myristate NN 542 552 13-acetate 13-acetate NN 553 554 ( ( ( 554 559 PMA)- PMA)- NNP 560 562 or or CC 563 574 TcR-derived tcr-derived JJ 575 582 signals signal NNS 583 590 induces induce VBZ 591 594 the the DT 595 603 enhanced enhance VBN 604 614 activation activation NN 615 617 of of IN 618 621 the the DT 622 635 transcription transcription NN 636 642 factor factor NN 643 651 NF-kappa NF-kappa NNP 652 654 B. B. NNP 655 659 Here here RB 660 662 we we PRP 663 669 report report VBP 670 674 that that IN 675 679 CD28 cd28 NN 680 690 engagement engagement NN 690 691 , , , 692 699 however however RB 699 700 , , , 701 707 exerts exert VBZ 708 716 opposite opposite JJ 717 724 effects effect NNS 725 727 on on IN 728 731 the the DT 732 745 transcription transcription NN 746 752 factor factor NN 753 757 AP-1 ap-1 NN 757 758 . . . 759 766 Whereas whereas IN 767 776 anti-CD28 anti-cd28 JJ 777 785 together together RB 786 790 with with IN 791 794 PMA PMA NNP 795 804 increased increase VBD 805 808 the the DT 809 812 DNA dna NN 813 820 binding binding NN 821 824 and and CC 825 841 trans-activation trans-activation NN 842 850 activity activity NN 851 853 of of IN 854 862 NF-kappa NF-kappa NNP 863 864 B B NNP 864 865 , , , 866 877 PMA-induced pma-induced JJ 878 888 activation activation NN 889 891 of of IN 892 896 AP-1 ap-1 NN 897 900 was be VBD 901 914 significantly significantly RB 915 925 suppressed suppress VBN 925 926 . . . 927 930 The the DT 931 941 inhibitory inhibitory JJ 942 948 effect effect NN 949 956 exerted exert VBN 957 959 by by IN 960 969 anti-CD28 anti-cd28 NN 970 973 was be VBD 974 982 observed observe VBN 983 985 at at IN 986 989 the the DT 990 995 level level NN 996 998 of of IN 999 1002 DNA DNA NNP 1003 1010 binding binding NN 1011 1013 as as RB 1014 1018 well well RB 1019 1021 as as IN 1022 1024 in in IN 1025 1035 functional functional JJ 1036 1049 reporter-gene reporter-gene JJ 1050 1056 assays assay NNS 1056 1057 . . . 1058 1063 These these DT 1064 1071 results result NNS 1072 1079 suggest suggest VBP 1080 1084 that that IN 1085 1088 the the DT 1089 1092 two two CD 1093 1106 transcription transcription NN 1107 1114 factors factor NNS 1115 1118 are be VBP 1119 1132 independently independently RB 1133 1142 regulated regulate VBN 1143 1146 and and CC 1147 1150 may may MD 1151 1158 perform perform VB 1159 1168 different different JJ 1169 1178 functions function NNS 1179 1185 during during IN 1186 1192 T-cell t-cell NN 1193 1203 activation activation NN 1203 1204 . . .