0 1 T t NN 2 6 cell cell NN 7 14 priming priming NN 15 23 enhances enhance VBZ 24 28 IL-4 il-4 NN 29 33 gene gene NN 34 44 expression expression NN 45 47 by by IN 48 58 increasing increase VBG 59 66 nuclear nuclear JJ 67 73 factor factor NN 74 76 of of IN 77 86 activated activate VBN 87 88 T t NN 89 94 cells cell NNS 94 95 . . . 97 100 The the DT 101 111 repetitive repetitive JJ 112 122 activation activation NN 123 125 of of IN 126 127 T t NN 128 133 cells cell NNS 134 135 ( ( ( 135 142 priming priming NN 142 143 ) ) ) 144 152 enhances enhance VBZ 153 156 the the DT 157 167 expression expression NN 168 170 of of IN 171 175 many many JJ 176 185 cytokines cytokine NNS 185 186 , , , 187 191 such such JJ 192 194 as as IN 195 199 IL-4 il-4 NN 199 200 , , , 201 204 but but CC 205 208 not not RB 209 215 others other NNS 215 216 , , , 217 221 such such JJ 222 224 as as IN 225 229 IL-2 il-2 NN 229 230 . . . 231 240 Molecular molecular JJ 241 251 mechanisms mechanism NNS 252 262 underlying underlie VBG 263 272 selective selective JJ 273 283 expression expression NN 284 286 of of IN 287 296 cytokines cytokine NNS 297 299 by by IN 300 301 T t NN 302 307 cells cell NNS 308 314 remain remain VBP 315 321 poorly poorly RB 322 332 understood understand VBN 332 333 . . . 334 338 Here here RB 339 341 we we PRP 342 346 show show VBP 347 351 that that IN 352 359 priming priming NN 360 362 of of IN 363 366 CD4 cd4 NN 367 368 T t NN 369 374 cells cell NNS 375 386 selectively selectively RB 387 395 enhances enhance VBZ 396 400 IL-4 il-4 NN 401 411 expression expression NN 412 420 relative relative JJ 421 423 to to TO 424 428 IL-2 il-2 NN 429 439 expression expression NN 440 442 by by IN 443 444 a a DT 445 460 transcriptional transcriptional JJ 461 470 mechanism mechanism NN 471 480 involving involve VBG 481 488 nuclear nuclear JJ 489 495 factor factor NN 496 498 of of IN 499 508 activated activate VBN 509 510 T t NN 511 516 cells cell NNS 517 518 ( ( ( 518 522 NFAT NFAT NNP 522 523 ) ) ) 524 532 proteins protein NNS 532 533 . . . 534 536 As as IN 537 545 detected detect VBN 546 548 by by IN 549 551 in in FW 552 556 vivo vivo FW 557 569 footprinting footprinting NN 569 570 , , , 571 578 priming priming NN 579 587 markedly markedly RB 588 597 increases increase VBZ 598 601 the the DT 602 622 activation-dependent activation-dependent JJ 623 633 engagement engagement NN 634 636 of of IN 637 640 the the DT 641 643 P0 p0 NN 644 647 and and CC 648 650 P1 p1 NN 651 663 NFAT-binding nfat-binding JJ 664 672 elements element NNS 673 675 of of IN 676 679 the the DT 680 684 IL-4 il-4 NN 685 693 promoter promoter NN 693 694 . . . 695 703 Moreover moreover RB 703 704 , , , 705 709 each each DT 710 718 proximal proximal JJ 719 720 P p NN 721 728 element element NN 729 731 is be VBZ 732 741 essential essential JJ 742 745 for for IN 746 753 optimal optimal JJ 754 758 IL-4 il-4 NN 759 767 promoter promoter NN 768 776 activity activity NN 776 777 . . . 778 787 Activated activate VBN 788 794 primed prim VBN 795 798 CD4 cd4 NN 799 800 T t NN 801 806 cells cell NNS 807 814 contain contain VBP 815 819 more more JJR 820 825 NFAT1 nfat1 NN 826 829 and and CC 830 837 support support VBP 838 845 greater great JJR 846 859 NFAT-directed nfat-directed JJ 860 873 transcription transcription NN 874 878 than than IN 879 887 unprimed unprimed JJ 888 891 CD4 cd4 NN 892 893 T t NN 894 899 cells cell NNS 899 900 , , , 901 906 while while IN 907 916 activator activator NN 917 924 protein protein NN 925 926 1 1 CD 927 934 binding binding NN 935 938 and and CC 939 948 activator activator NN 949 956 protein protein NN 957 967 1-mediated 1-mediated JJ 968 981 transcription transcription NN 982 984 by by IN 985 989 both both DT 990 994 cell cell NN 995 1000 types type NNS 1001 1003 is be VBZ 1004 1011 similar similar JJ 1011 1012 . . . 1013 1022 Increased increase VBN 1023 1033 expression expression NN 1034 1036 of of IN 1037 1046 wild-type wild-type JJ 1047 1052 NFAT1 nfat1 NN 1053 1066 substantially substantially RB 1067 1076 increases increase VBZ 1077 1081 IL-4 il-4 NN 1082 1090 promoter promoter NN 1091 1099 activity activity NN 1100 1102 in in IN 1103 1111 unprimed unprimed JJ 1112 1115 CD4 cd4 NN 1116 1117 T t NN 1118 1123 cells cell NNS 1123 1124 , , , 1125 1135 suggesting suggest VBG 1136 1141 NFAT1 nfat1 NN 1142 1145 may may MD 1146 1148 be be VB 1149 1157 limiting limit VBG 1158 1161 for for IN 1162 1166 IL-4 il-4 NN 1167 1171 gene gene NN 1172 1182 expression expression NN 1183 1185 in in IN 1186 1190 this this DT 1191 1195 cell cell NN 1196 1200 type type NN 1200 1201 . . . 1202 1213 Furthermore furthermore RB 1213 1214 , , , 1215 1216 a a DT 1217 1226 truncated truncate VBN 1227 1231 form form NN 1232 1234 of of IN 1235 1240 NFAT1 nfat1 NN 1241 1245 acts act VBZ 1246 1248 as as IN 1249 1250 a a DT 1251 1268 dominant-negative dominant-negative JJ 1268 1269 , , , 1270 1278 reducing reduce VBG 1279 1283 IL-4 il-4 NN 1284 1292 promoter promoter NN 1293 1301 activity activity NN 1302 1304 in in IN 1305 1311 primed prim VBN 1312 1315 CD4 cd4 NN 1316 1317 T t NN 1318 1323 cells cell NNS 1324 1327 and and CC 1328 1338 confirming confirm VBG 1339 1342 the the DT 1343 1353 importance importance NN 1354 1356 of of IN 1357 1367 endogenous endogenous JJ 1368 1372 NFAT nfat NN 1373 1375 to to TO 1376 1385 increased increase VBN 1386 1390 IL-4 il-4 NN 1391 1395 gene gene NN 1396 1406 expression expression NN 1407 1409 by by IN 1410 1418 effector effector NN 1419 1420 T t NN 1421 1426 cells cell NNS 1426 1427 . . . 1428 1433 NFAT1 NFAT1 NNP 1434 1441 appears appear VBZ 1442 1444 to to TO 1445 1447 be be VB 1448 1451 the the DT 1452 1457 major major JJ 1458 1462 NFAT NFAT NNP 1463 1469 family family NN 1470 1476 member member NN 1477 1488 responsible responsible JJ 1489 1492 for for IN 1493 1496 the the DT 1497 1504 initial initial JJ 1505 1514 increased increase VBN 1515 1525 expression expression NN 1526 1528 of of IN 1529 1533 IL-4 il-4 NN 1534 1536 by by IN 1537 1543 primed prim VBN 1544 1547 CD4 cd4 NN 1548 1549 T t NN 1550 1555 cells cell NNS 1555 1556 . . .