0 1 T t NN 2 8 helper helper NN 9 24 differentiation differentiation NN 25 33 proceeds proceed VBZ 34 41 through through IN 42 57 Stat1-dependent stat1-dependent JJ 57 58 , , , 59 74 Stat4-dependent stat4-dependent JJ 75 78 and and CC 79 96 Stat4-independent stat4-independent JJ 97 103 phases phase NNS 103 104 . . . 106 110 Much much JJ 111 113 of of IN 114 117 our our PRP$ 118 123 focus focus NN 124 126 in in IN 127 140 understanding understand VBG 141 148 Th1/Th2 th1/th2 NN 149 160 development development NN 161 164 has have VBZ 165 169 been be VBN 170 172 on on IN 173 176 the the DT 177 184 signals signal NNS 185 194 delivered deliver VBN 195 197 by by IN 198 203 IL-12 il-12 NN 204 207 and and CC 208 212 IL-4 il-4 NN 213 215 as as IN 216 221 final final JJ 222 234 determinants determinant NNS 235 237 of of IN 238 246 terminal terminal JJ 247 248 T t NN 249 253 cell cell NN 254 269 differentiation differentiation NN 269 270 . . . 271 278 Because because IN 279 289 extinction extinction NN 290 292 of of IN 293 298 IL-12 il-12 NN 299 308 signaling signaling NN 309 311 in in IN 312 317 early early JJ 318 321 Th2 th2 NN 322 333 development development NN 334 339 could could MD 340 351 potentially potentially RB 352 354 be be VB 355 364 important important JJ 365 367 in in IN 368 378 imprinting imprint VBG 379 380 a a DT 381 385 more more RBR 386 395 permanent permanent JJ 396 399 Th2 th2 NN 400 409 phenotype phenotype NN 410 412 on on IN 413 414 a a DT 415 425 population population NN 426 428 of of IN 429 430 T t NN 431 436 cells cell NNS 436 437 , , , 438 440 we we PRP 441 445 have have VBP 446 450 also also RB 451 459 examined examine VBN 460 467 various various JJ 468 478 parameters parameter NNS 479 489 regulating regulate VBG 490 493 the the DT 494 499 IL-12 il-12 NN 500 509 signaling signaling NN 510 517 pathway pathway NN 517 518 . . . 519 526 Whereas whereas IN 527 531 IL-4 il-4 NN 532 539 appears appear VBZ 540 542 to to TO 543 550 repress repress VB 551 561 functional functional JJ 562 567 IL-12 il-12 NN 568 577 signaling signaling NN 578 585 through through IN 586 596 inhibition inhibition NN 597 599 of of IN 600 606 IL-12R IL-12R NNP 607 611 beta beta NN 612 613 2 2 CD 614 624 expression expression NN 624 625 , , , 626 635 IFN-gamma IFN-gamma NNP 636 638 in in IN 639 642 the the DT 643 648 mouse mouse NN 648 649 , , , 650 653 and and CC 654 663 IFN-alpha IFN-alpha NNP 664 666 in in IN 667 670 the the DT 671 676 human human JJ 677 683 appear appear NN 684 686 to to TO 687 693 induce induce VB 694 700 IL-12R il-12r NN 701 705 beta beta NN 706 707 2 2 CD 708 718 expression expression NN 719 722 and and CC 723 730 promote promote VB 731 736 IL-12 il-12 NN 737 751 responsiveness responsiveness NN 751 752 . . . 753 755 We we PRP 756 763 propose propose VBP 764 768 that that IN 769 772 Th1 th1 NN 773 784 development development NN 785 788 can can MD 789 791 be be VB 792 802 considered consider VBN 803 805 in in IN 806 809 two two CD 810 816 stages stage NNS 816 817 , , , 818 829 capacitance capacitance NN 830 833 and and CC 834 845 development development NN 845 846 . . . 847 858 Capacitance Capacitance NNP 859 864 would would MD 865 871 simply simply RB 872 879 involve involve VB 880 890 expression expression NN 891 893 of of IN 894 900 IL-12R IL-12R NNP 901 905 beta beta NN 906 907 1 1 CD 908 911 and and CC 912 916 beta beta SYM 917 918 2 2 CD 919 927 subunits subunit NNS 927 928 , , , 929 938 regulated regulate VBN 939 941 by by IN 942 945 TCR TCR NNP 945 946 , , , 947 951 IL-4 il-4 NN 952 955 and and CC 956 960 IFNs ifn NNS 960 961 . . . 962 965 The the DT 966 972 second second JJ 973 978 stage stage NN 978 979 , , , 980 991 development development NN 991 992 , , , 993 995 we we PRP 996 1003 propose propose VBP 1004 1006 is be VBZ 1007 1010 the the DT 1011 1015 true true JJ 1016 1021 IL-12 il-12 NN 1022 1029 induced induce VBD 1030 1043 developmental developmental JJ 1044 1049 stage stage NN 1049 1050 , , , 1051 1060 involving involve VBG 1061 1071 expression expression NN 1072 1074 of of IN 1075 1080 Stat4 stat4 NN 1081 1090 inducible inducible JJ 1091 1099 proteins protein NNS 1099 1100 . . . 1101 1103 In in IN 1104 1107 the the DT 1108 1113 human human JJ 1113 1114 , , , 1115 1119 this this DT 1120 1123 may may MD 1124 1128 also also RB 1129 1134 occur occur VB 1135 1138 via via IN 1139 1148 IFN-alpha IFN-alpha NNP 1148 1149 , , , 1150 1155 which which WDT 1156 1158 is be VBZ 1159 1163 able able JJ 1164 1166 to to TO 1167 1175 activate activate VB 1176 1181 Stat4 Stat4 NNP 1181 1182 . . . 1183 1185 It it PRP 1186 1188 is be VBZ 1189 1196 perhaps perhaps RB 1197 1205 possible possible JJ 1206 1210 that that IN 1211 1214 all all DT 1215 1217 of of IN 1218 1223 Stat4 stat4 NN 1224 1231 actions action NNS 1232 1234 on on IN 1235 1238 Th1 th1 NN 1239 1250 development development NN 1251 1254 may may MD 1255 1257 be be VB 1258 1263 exert exert VBN 1264 1272 directly directly RB 1273 1275 by by IN 1276 1281 Stat4 stat4 NN 1282 1284 at at IN 1285 1288 the the DT 1289 1298 IFN-gamma IFN-gamma NNP 1299 1303 gene gene NN 1303 1304 , , , 1305 1312 however however RB 1313 1315 we we PRP 1316 1323 suggest suggest VBP 1324 1328 that that IN 1328 1329 , , , 1330 1334 more more RBR 1335 1341 likely likely JJ 1341 1342 , , , 1343 1348 Stat4 stat4 NN 1349 1352 may may MD 1353 1356 act act VB 1357 1359 to to TO 1360 1366 induce induce VB 1367 1370 Th1 th1 NN 1371 1382 development development NN 1383 1390 through through IN 1391 1394 the the DT 1395 1404 induction induction NN 1405 1407 of of IN 1408 1413 other other JJ 1414 1426 non-cytokine non-cytokine JJ 1427 1432 genes gene NNS 1432 1433 , , , 1434 1439 whose whose WP$ 1440 1446 stable stable JJ 1447 1457 expression expression NN 1458 1467 maintains maintain VBZ 1468 1471 the the DT 1472 1487 transcriptional transcriptional JJ 1488 1493 state state NN 1494 1496 of of IN 1497 1498 a a DT 1499 1502 Th1 th1 NN 1503 1507 cell cell NN 1507 1508 . . .