0 10 Activation Activation NNP 11 13 of of IN 14 17 the the DT 18 24 signal signal NN 25 35 transducer transducer NN 36 39 and and CC 40 53 transcription transcription NN 54 55 ( ( ( 55 59 STAT STAT NNP 59 60 ) ) ) 61 70 signaling signaling NN 71 78 pathway pathway NN 79 81 in in IN 82 83 a a DT 84 91 primary primary JJ 92 93 T t NN 94 98 cell cell NN 99 107 response response NN 107 108 . . . 109 117 Critical critical JJ 118 122 role role NN 123 126 for for IN 127 131 IL-6 IL-6 NNP 131 132 . . . 134 137 The the DT 138 139 T t NN 140 144 cell cell NN 145 155 activation activation NN 156 158 is be VBZ 159 168 initiated initiate VBN 169 171 by by IN 172 183 interaction interaction NN 184 186 of of IN 187 195 specific specific JJ 196 199 Ags ag NNS 200 204 with with IN 205 208 TCR TCR NNP 208 209 , , , 210 218 followed follow VBN 219 221 by by IN 222 232 activation activation NN 233 235 of of IN 236 249 intracellular intracellular JJ 250 261 biochemical biochemical JJ 262 268 events event NNS 269 276 leading lead VBG 277 279 to to TO 280 290 activation activation NN 291 293 of of IN 294 301 several several JJ 302 307 genes gene NNS 307 308 . . . 309 312 The the DT 313 323 activation activation NN 324 326 of of IN 327 333 signal signal NN 334 344 transducer transducer NN 345 348 and and CC 349 358 activator activator NN 359 361 of of IN 362 375 transcription transcription NN 376 377 ( ( ( 377 381 STAT STAT NNP 381 382 ) ) ) 383 391 proteins protein NNS 392 394 in in IN 395 396 a a DT 397 404 primary primary JJ 405 417 TCR-mediated tcr-mediated JJ 418 428 activation activation NN 429 431 of of IN 432 433 T t NN 434 439 cells cell NNS 440 444 have have VBP 445 449 been be VBN 450 458 explored explore VBN 458 459 . . . 460 462 In in IN 463 471 purified purify VBN 472 477 human human JJ 478 488 peripheral peripheral JJ 489 494 blood blood NN 495 496 T t NN 497 502 cells cell NNS 502 503 , , , 504 511 nuclear nuclear JJ 512 516 STAT STAT NNP 517 525 proteins protein NNS 526 530 were be VBD 531 540 activated activate VBN 541 554 approximately approximately RB 555 556 3 3 CD 557 558 h h NN 559 564 after after IN 565 575 activation activation NN 576 578 by by IN 579 591 cross-linked cross-linked JJ 592 600 anti-CD3 anti-cd3 JJ 601 604 Abs ab NNS 604 605 . . . 606 611 These these DT 612 616 STAT STAT NNP 617 625 proteins protein NNS 626 630 were be VBD 631 639 detected detect VBN 640 642 by by IN 643 648 using use VBG 649 652 the the DT 653 672 IFN-gamma-activated ifn-gamma-activated JJ 673 681 sequence sequence NN 682 683 ( ( ( 683 686 GAS GAS NNP 686 687 ) ) ) 688 691 and and CC 692 699 related related JJ 700 716 oligonucleotides oligonucleotide NNS 717 719 as as IN 720 726 probes probe NNS 727 729 in in IN 730 745 electrophoretic electrophoretic JJ 746 754 mobility mobility NN 755 760 shift shift NN 761 766 assay assay NN 766 767 . . . 768 776 Analysis Analysis NNP 777 779 of of IN 780 783 the the DT 784 791 nuclear nuclear JJ 792 800 extracts extract NNS 801 805 with with IN 806 815 anti-STAT anti-stat JJ 816 819 Abs ab NNS 820 829 indicated indicate VBD 830 834 that that IN 835 839 they they PRP 840 849 contained contain VBD 850 856 STAT-3 stat-3 NN 857 860 and and CC 861 871 additional additional JJ 872 880 proteins protein NNS 881 894 crossreactive crossreactive JJ 895 899 with with IN 900 903 the the DT 904 908 STAT STAT NNP 909 915 family family NN 915 916 . . . 917 920 The the DT 921 930 induction induction NN 931 933 of of IN 934 938 STAT STAT NNP 939 947 activity activity NN 948 951 was be VBD 952 961 inhibited inhibit VBN 962 972 completely completely RB 973 975 by by IN 976 988 pretreatment pretreatment NN 989 993 with with IN 994 1000 either either CC 1001 1014 cycloheximide cycloheximide NN 1015 1017 or or CC 1018 1029 cyclosporin cyclosporin NN 1030 1031 A a NN 1031 1032 , , , 1033 1037 thus thus RB 1038 1048 indicating indicate VBG 1049 1053 that that IN 1054 1057 the the DT 1058 1067 induction induction NN 1068 1071 was be VBD 1072 1075 due due JJ 1076 1078 to to TO 1079 1080 a a DT 1081 1090 secondary secondary JJ 1091 1097 factor factor NN 1098 1106 produced produce VBN 1107 1109 by by IN 1110 1113 the the DT 1114 1123 activated activate VBN 1124 1125 T t NN 1126 1131 cells cell NNS 1131 1132 . . . 1133 1135 As as IN 1136 1148 neutralizing neutralize VBG 1149 1158 anti-IL-6 anti-il-6 NN 1159 1162 Abs ab NNS 1163 1174 effectively effectively RB 1175 1189 down-regulated down-regulate VBD 1190 1193 the the DT 1194 1199 early early JJ 1200 1209 induction induction NN 1210 1212 of of IN 1213 1217 STAT STAT NNP 1218 1226 proteins protein NNS 1227 1230 and and CC 1231 1233 as as IN 1234 1245 exogenously exogenously RB 1246 1251 added add VBN 1252 1256 IL-6 il-6 NN 1257 1264 rapidly rapidly RB 1265 1274 activated activate VBD 1275 1278 DNA dna NN 1279 1286 binding binding NN 1287 1294 similar similar JJ 1295 1297 to to TO 1298 1310 TCR-mediated tcr-mediated JJ 1311 1319 bindings binding NNS 1319 1320 , , , 1321 1323 it it PRP 1324 1327 can can MD 1328 1330 be be VB 1331 1340 concluded conclude VBN 1341 1345 that that IN 1346 1350 IL-6 IL-6 NNP 1351 1353 is be VBZ 1354 1357 the the DT 1358 1364 factor factor NN 1365 1376 responsible responsible JJ 1377 1380 for for IN 1381 1384 the the DT 1385 1395 activation activation NN 1396 1398 of of IN 1399 1403 STAT stat NN 1404 1412 proteins protein NNS 1413 1415 in in IN 1416 1417 a a DT 1418 1425 primary primary JJ 1426 1427 T t NN 1428 1432 cell cell NN 1433 1441 response response NN 1441 1442 . . .