0 10 Activation Activation NNP 11 13 of of IN 14 24 lymphokine lymphokine NN 25 30 genes gene NNS 31 33 in in IN 34 35 T t NN 36 41 cells cell NNS 41 42 : : : 43 47 role role NN 48 50 of of IN 51 61 cis-acting cis-acting JJ 62 65 DNA dna NN 66 74 elements element NNS 75 79 that that WDT 80 87 respond respond VBP 88 90 to to TO 91 92 T t NN 93 97 cell cell NN 98 108 activation activation NN 109 116 signals signal NNS 116 117 . . . 119 129 Activation Activation NNP 130 132 of of IN 133 134 T t NN 135 140 cells cell NNS 141 143 is be VBZ 144 153 initiated initiate VBN 154 156 by by IN 157 160 the the DT 161 172 recognition recognition NN 173 175 of of IN 176 183 antigen antigen NN 184 186 on on IN 187 194 antigen antigen NN 195 205 presenting presenting NN 206 211 cells cell NNS 212 214 to to TO 215 220 exert exert VB 221 224 the the DT 225 233 effector effector NN 234 243 functions function NNS 244 246 in in IN 247 253 immune immune JJ 254 257 and and CC 258 270 inflammatory inflammatory JJ 271 280 responses response NNS 280 281 . . . 282 285 Two two CD 286 291 types type NNS 292 294 of of IN 295 301 helper helper NN 302 303 T t NN 304 308 cell cell NN 309 310 ( ( ( 310 312 Th Th NNP 312 313 ) ) ) 314 320 clones clone NNS 321 322 ( ( ( 322 325 Th1 Th1 NNP 326 329 and and CC 330 333 Th2 Th2 NNP 333 334 ) ) ) 335 338 are be VBP 339 346 defined define VBN 347 349 on on IN 350 353 the the DT 354 359 basis basis NN 360 362 of of IN 363 372 different different JJ 373 381 patterns pattern NNS 382 384 of of IN 385 393 cytokine cytokine NN 394 395 ( ( ( 395 405 lymphokine lymphokine NN 405 406 ) ) ) 407 416 secretion secretion NN 416 417 . . . 418 422 They they PRP 423 432 determine determine VBP 433 436 the the DT 437 444 outcome outcome NN 445 447 of of IN 448 450 an an DT 451 460 antigenic antigenic JJ 461 469 response response NN 470 476 toward toward IN 477 484 humoral humoral JJ 485 487 or or CC 488 501 cell-mediated cell-mediated JJ 502 510 immunity immunity NN 510 511 . . . 512 520 Although although IN 521 531 lymphokine lymphokine NN 532 537 genes gene NNS 538 541 are be VBP 542 554 coordinately coordinately RB 555 564 regulated regulate VBN 565 569 upon upon IN 570 577 antigen antigen NN 578 589 stimulation stimulation NN 589 590 , , , 591 595 they they PRP 596 599 are be VBP 600 609 regulated regulate VBN 610 612 by by IN 613 616 the the DT 617 627 mechanisms mechanism NNS 628 634 common common JJ 635 637 to to TO 638 641 all all DT 642 644 as as RB 645 649 well well RB 650 652 as as IN 653 658 those those DT 659 664 which which WDT 665 668 are be VBP 669 675 unique unique JJ 676 678 to to TO 679 683 each each DT 684 688 gene gene NN 688 689 . . . 690 693 For for IN 694 698 most most JJS 699 709 lymphokine lymphokine NN 710 715 genes gene NNS 715 716 , , , 717 718 a a DT 719 730 combination combination NN 731 733 of of IN 734 741 phorbol phorbol NN 742 748 esters ester NNS 749 750 ( ( ( 750 757 phorbol phorbol NN 758 770 12-myristate 12-myristate NN 771 773 13 13 CD 774 781 acetate acetate NN 781 782 , , , 783 786 PMA PMA NNP 786 787 ) ) ) 788 791 and and CC 792 799 calcium calcium NN 800 810 ionophores ionophore NNS 811 812 ( ( ( 812 818 A23187 A23187 NNP 818 819 ) ) ) 820 822 is be VBZ 823 831 required require VBN 832 835 for for IN 836 841 their their PRP$ 842 849 maximal maximal JJ 850 859 induction induction NN 859 860 . . . 861 864 Yet yet RB 865 872 phorbol phorbol NN 873 878 ester ester NN 879 884 alone alone RB 885 887 or or CC 888 895 calcium calcium NN 896 905 ionophore ionophore NN 906 911 alone alone RB 912 919 produce produce VBP 920 927 several several JJ 928 939 lymphokines lymphokine NNS 939 940 . . . 941 944 The the DT 945 955 production production NN 956 958 of of IN 959 962 the the DT 963 985 granulocyte-macrophage granulocyte-macrophage JJ 986 992 colony colony NN 993 1004 stimulating stimulating NN 1005 1011 factor factor NN 1012 1013 ( ( ( 1013 1019 GM-CSF GM-CSF NNP 1019 1020 ) ) ) 1021 1023 is be VBZ 1024 1034 completely completely RB 1035 1044 dependent dependent JJ 1045 1047 on on IN 1048 1051 the the DT 1052 1055 two two CD 1056 1063 signals signal NNS 1063 1064 . . . 1065 1067 We we PRP 1068 1072 have have VBP 1073 1083 previously previously RB 1084 1089 found find VBN 1090 1091 a a DT 1092 1102 cis-acting cis-acting JJ 1103 1109 region region NN 1110 1118 spanning span VBG 1119 1122 the the DT 1123 1129 GM-CSF GM-CSF NNP 1130 1138 promoter promoter NN 1139 1145 region region NN 1146 1147 ( ( ( 1147 1156 positions position NNS 1157 1160 -95 -95 CD 1161 1163 to to TO 1164 1167 +27 +27 CD 1167 1168 ) ) ) 1169 1173 that that WDT 1174 1181 confers confer VBZ 1182 1194 inducibility inducibility NN 1195 1197 to to TO 1198 1206 reporter reporter NN 1207 1212 genes gene NNS 1213 1215 in in IN 1216 1225 transient transient JJ 1226 1238 transfection transfection NN 1239 1245 assays assay NNS 1245 1246 . . . 1247 1254 Further further JJ 1255 1263 analysis analysis NN 1264 1274 identified identify VBD 1275 1280 three three CD 1281 1289 elements element NNS 1290 1298 required require VBN 1299 1302 for for IN 1303 1312 efficient efficient JJ 1313 1322 induction induction NN 1322 1323 , , , 1324 1332 referred refer VBN 1333 1335 to to TO 1336 1338 as as IN 1339 1342 GM2 gm2 NN 1342 1343 , , , 1344 1350 GC-box gc-box NN 1351 1354 and and CC 1355 1364 conserved conserve VBN 1365 1375 lymphokine lymphokine NN 1376 1383 element element NN 1384 1385 ( ( ( 1385 1389 CLE0 CLE0 NNP 1389 1390 ) ) ) 1390 1391 . . . 1392 1395 GM2 GM2 NNP 1396 1403 defines define VBZ 1404 1405 a a DT 1406 1413 binding bind VBG 1414 1418 site site NN 1419 1422 for for IN 1423 1433 protein(s) protein(s) NN 1434 1439 whose whose WP$ 1440 1447 binding binding NN 1448 1450 is be VBZ 1451 1460 inducible inducible JJ 1461 1463 by by IN 1464 1467 PMA PMA NNP 1467 1468 . . . 1469 1472 One one CD 1473 1480 protein protein NN 1480 1481 , , , 1482 1488 NF-GM2 nf-gm2 NN 1489 1491 is be VBZ 1492 1499 similar similar JJ 1500 1502 to to TO 1503 1506 the the DT 1507 1520 transcription transcription NN 1521 1527 factor factor NN 1528 1533 NF-kB nf-kb NN 1533 1534 . . . 1535 1541 GC-box GC-box NNP 1542 1544 is be VBZ 1545 1546 a a DT 1547 1554 binding bind VBG 1555 1559 site site NN 1560 1563 for for IN 1564 1578 constitutively constitutively RB 1579 1584 bound bind VBN 1585 1593 proteins protein NNS 1593 1594 . . . 1595 1599 CLEO cleo NN 1600 1607 defines define VBZ 1608 1609 a a DT 1610 1617 binding bind VBG 1618 1622 site site NN 1623 1626 for for IN 1627 1637 protein(s) protein(s) NN 1638 1643 whose whose WP$ 1644 1651 optimum optimum JJ 1652 1659 binding binding NN 1660 1662 is be VBZ 1663 1673 stimulated stimulate VBN 1674 1676 by by IN 1677 1680 PMA PMA NNP 1681 1684 and and CC 1685 1691 A23187 A23187 NNP 1691 1692 . . . 1693 1698 Viral viral JJ 1699 1715 trans-activators trans-activator NNS 1716 1720 such such JJ 1721 1723 as as IN 1724 1727 Tax Tax NNP 1728 1729 ( ( ( 1729 1734 human human JJ 1735 1736 T t NN 1737 1741 cell cell NN 1742 1750 leukemia leukemia NN 1751 1758 virus-1 virus-1 NN 1758 1759 , , , 1760 1766 HTLV-1 HTLV-1 NNP 1766 1767 ) ) ) 1768 1771 and and CC 1772 1774 E2 e2 NN 1775 1776 ( ( ( 1776 1782 bovine bovine JJ 1783 1792 papilloma papilloma NN 1793 1798 virus virus NN 1798 1799 , , , 1800 1803 BPV BPV NNP 1803 1804 ) ) ) 1805 1813 proteins protein NNS 1814 1817 are be VBP 1818 1823 other other JJ 1824 1830 agents agent NNS 1831 1836 which which WDT 1837 1845 activate activate VBP 1846 1856 lymphokine lymphokine NN 1857 1861 gene gene NN 1862 1872 expression expression NN 1873 1875 by by IN 1876 1885 bypassing bypass VBG 1886 1887 T t NN 1888 1892 cell cell NN 1893 1901 receptor receptor NN 1902 1903 ( ( ( 1903 1906 TCR TCR NNP 1906 1907 ) ) ) 1908 1916 mediated mediated JJ 1917 1926 signaling signaling NN 1926 1927 . . . 1928 1931 The the DT 1932 1948 trans-activation trans-activation NN 1949 1955 domain domain NN 1956 1958 of of IN 1959 1961 E2 E2 NNP 1962 1965 and and CC 1966 1969 Tax Tax NNP 1970 1972 is be VBZ 1973 1988 interchangeable interchangeable JJ 1989 1997 although although IN 1998 2002 they they PRP 2003 2007 have have VBP 2008 2010 no no DT 2011 2018 obvious obvious JJ 2019 2027 sequence sequence NN 2028 2036 homology homology NN 2037 2044 between between IN 2045 2049 them them PRP 2049 2050 . . . 2051 2054 The the DT 2055 2060 viral viral JJ 2061 2077 trans-activators trans-activator NNS 2078 2084 appear appear VBP 2085 2087 to to TO 2088 2094 target target VB 2095 2103 specific specific JJ 2104 2107 DNA dna NN 2108 2115 binding binding NN 2116 2123 protein protein NN 2124 2128 such such JJ 2129 2131 as as IN 2132 2137 NF-kB NF-kB NNP 2138 2141 and and CC 2142 2145 Sp1 sp1 NN 2146 2148 to to TO 2149 2159 cis-acting cis-acting JJ 2160 2163 DNA dna NN 2164 2168 site site NN 2169 2172 and and CC 2173 2180 promote promote VB 2181 2191 lymphokine lymphokine NN 2192 2196 gene gene NN 2197 2207 expression expression NN 2208 2215 without without IN 2216 2228 TCR-mediated tcr-mediated JJ 2229 2240 stimulation stimulation NN 2240 2241 . . .