0 10 Modulation modulation NN 11 13 of of IN 14 17 the the DT 18 28 expression expression NN 29 31 of of IN 32 35 the the DT 36 45 IFN-gamma IFN-gamma NNP 46 54 receptor receptor NN 55 65 beta-chain beta-chain NN 66 74 controls control VBZ 75 89 responsiveness responsiveness NN 90 92 to to TO 93 102 IFN-gamma IFN-gamma NNP 103 105 in in IN 106 111 human human JJ 112 122 peripheral peripheral JJ 123 128 blood blood NN 129 130 T t NN 131 136 cells cell NNS 136 137 . . . 139 148 IFN-gamma IFN-gamma NNP 149 152 has have VBZ 153 159 potent potent JJ 160 177 antiproliferative antiproliferative JJ 178 181 and and CC 182 191 apoptotic apoptotic JJ 192 199 effects effect NNS 200 202 in in IN 203 204 T t NN 205 210 cells cell NNS 211 215 that that WDT 216 219 are be VBP 220 229 important important JJ 230 232 in in IN 233 244 determining determine VBG 245 246 T t NN 247 251 cell cell NN 252 263 development development NN 264 267 and and CC 268 277 polarized polarize VBN 278 293 differentiation differentiation NN 293 294 . . . 295 304 Therefore therefore RB 304 305 , , , 306 309 any any DT 310 315 event event NN 316 320 that that WDT 321 328 enables enable VBZ 329 330 T t NN 331 336 cells cell NNS 337 339 to to TO 340 346 become become VB 347 351 less less RBR 352 362 responsive responsive JJ 363 365 to to TO 366 370 IFN- ifn- NN 371 376 gamma gamma NN 377 380 may may MD 381 392 potentially potentially RB 393 398 alter alter VB 399 405 immune immune JJ 406 420 responsiveness responsiveness NN 421 423 to to TO 424 426 Ag Ag NNP 426 427 . . . 428 430 In in IN 431 435 this this DT 436 440 work work NN 440 441 , , , 442 444 we we PRP 445 449 show show VBP 450 454 that that IN 455 460 human human JJ 461 471 peripheral peripheral JJ 472 477 blood blood NN 478 479 T t NN 480 485 cells cell NNS 486 490 that that WDT 491 494 are be VBP 495 505 stimulated stimulate VBN 506 513 through through IN 514 517 the the DT 518 521 TCR TCR NNP 522 525 and and CC 526 534 expanded expand VBN 535 539 with with IN 540 544 IL-2 il-2 NN 545 548 are be VBP 549 561 unresponsive unresponsive JJ 562 564 to to TO 565 574 IFN-gamma IFN-gamma NNP 574 575 , , , 576 578 as as IN 579 589 determined determine VBN 590 592 by by IN 593 594 a a DT 595 599 lack lack NN 600 602 of of IN 603 613 activation activation NN 614 616 of of IN 617 620 jak jak NN 621 628 kinases kinase NNS 629 632 and and CC 633 636 the the DT 637 650 transcription transcription NN 651 657 factor factor NN 657 658 , , , 659 671 STAT1(alpha) STAT1(alpha) NNP 671 672 , , , 673 674 a a DT 675 681 signal signal NN 682 692 transducer transducer NN 693 696 and and CC 697 706 activator activator NN 707 709 of of IN 710 723 transcription transcription NN 723 724 . . . 725 729 This this DT 730 747 nonresponsiveness nonresponsiveness NN 748 754 occurs occur VBZ 755 762 because because IN 763 765 of of IN 766 767 a a DT 768 772 lack lack NN 773 775 of of IN 776 786 expression expression NN 787 789 of of IN 790 793 the the DT 794 799 beta- beta- NN 800 805 chain chain NN 806 807 ( ( ( 807 816 accessory accessory JJ 817 823 factor factor NN 823 824 ) ) ) 825 827 of of IN 828 831 the the DT 832 841 IFN-gamma IFN-gamma NNP 842 850 receptor receptor NN 850 851 , , , 852 857 while while IN 858 860 at at IN 861 864 the the DT 865 869 same same JJ 870 874 time time NN 875 886 maintaining maintain VBG 887 896 IFN-gamma IFN-gamma NNP 897 905 receptor receptor NN 906 917 alpha-chain alpha-chain NN 918 928 expression expression NN 928 929 . . . 930 940 Expression expression NN 941 943 of of IN 944 947 the the DT 948 958 beta-chain beta-chain NN 959 962 can can MD 963 965 be be VB 966 974 restored restore VBN 975 977 by by IN 978 987 secondary secondary JJ 988 991 TCR TCR NNP 992 1000 ligation ligation NN 1001 1003 or or CC 1004 1007 PMA PMA NNP 1008 1017 treatment treatment NN 1017 1018 . . . 1019 1020 T t NN 1021 1025 cell cell NN 1026 1032 blasts blast NNS 1033 1040 treated treat VBN 1041 1045 with with IN 1046 1049 PMA PMA NNP 1050 1053 are be VBP 1054 1057 now now RB 1058 1068 responsive responsive JJ 1069 1071 to to TO 1072 1081 IFN-gamma IFN-gamma NNP 1081 1082 . . . 1083 1087 When when WRB 1088 1095 freshly freshly RB 1096 1104 isolated isolate VBN 1104 1105 , , , 1106 1112 highly highly RB 1113 1121 enriched enrich VBN 1122 1123 ( ( ( 1123 1126 >98 >98 CD 1126 1127 % % NN 1127 1128 ) ) ) 1129 1130 T t NN 1131 1136 cells cell NNS 1137 1140 are be VBP 1141 1149 examined examine VBN 1150 1153 for for IN 1154 1163 IFN-gamma IFN-gamma NNP 1164 1178 responsiveness responsiveness NN 1178 1179 ; ; : 1180 1185 these these DT 1186 1191 cells cell NNS 1192 1195 can can MD 1196 1203 respond respond VB 1204 1206 to to TO 1207 1216 IFN-gamma IFN-gamma NNP 1217 1220 and and CC 1221 1228 express express VB 1229 1239 beta-chain beta-chain NN 1239 1240 . . . 1241 1250 Therefore therefore RB 1250 1251 , , , 1252 1254 as as IN 1255 1256 T t NN 1257 1262 cells cell NNS 1263 1271 progress progress VBP 1272 1276 from from IN 1277 1284 primary primary JJ 1285 1288 TCR TCR NNP 1289 1299 activation activation NN 1300 1307 through through IN 1308 1322 IL-2-dependent il-2-dependent JJ 1323 1336 proliferation proliferation NN 1336 1337 , , , 1338 1346 followed follow VBN 1347 1349 by by IN 1350 1359 secondary secondary JJ 1360 1363 TCR TCR NNP 1364 1375 stimulation stimulation NN 1375 1376 , , , 1377 1382 their their PRP$ 1383 1397 responsiveness responsiveness NN 1398 1400 to to TO 1401 1410 IFN-gamma IFN-gamma NNP 1411 1417 varies vary VBZ 1417 1418 , , , 1419 1422 and and CC 1423 1427 this this DT 1428 1431 may may MD 1432 1438 affect affect VB 1439 1444 their their PRP$ 1445 1452 ability ability NN 1453 1455 to to TO 1456 1467 participate participate VB 1468 1470 in in IN 1471 1473 an an DT 1474 1481 ongoing ongoing JJ 1482 1488 immune immune JJ 1489 1497 response response NN 1497 1498 . . .