0 6 GM-CSF GM-CSF NNP 7 10 and and CC 11 15 IL-2 il-2 NN 16 21 share share VBP 22 28 common common JJ 29 36 control control NN 37 47 mechanisms mechanism NNS 48 50 in in IN 51 59 response response NN 60 62 to to TO 63 76 costimulatory costimulatory JJ 77 84 signals signal NNS 85 87 in in IN 88 89 T t NN 90 95 cells cell NNS 95 96 . . . 98 105 Antigen antigen NN 106 115 complexed complexe VBN 116 120 with with IN 121 126 major major JJ 127 145 histocompatibility histocompatibility NN 146 153 complex complex NN 154 159 class class NN 160 161 I i CD 162 164 or or CC 165 167 II ii CD 168 177 molecules molecule NNS 178 180 on on IN 181 184 the the DT 185 192 surface surface NN 193 195 of of IN 196 203 antigen antigen NN 204 214 presenting presenting NN 215 220 cells cell NNS 221 230 interacts interact VBZ 231 235 with with IN 236 239 the the DT 240 241 T t NN 242 246 cell cell NN 247 255 receptor receptor NN 256 257 ( ( ( 257 260 TCR TCR NNP 260 261 ) ) ) 262 264 on on IN 265 268 the the DT 269 276 surface surface NN 277 279 of of IN 280 281 T t NN 282 287 cells cell NNS 288 291 and and CC 292 301 initiates initiate VBZ 302 304 an an DT 305 315 activation activation NN 316 323 cascade cascade NN 323 324 . . . 325 327 So so RB 328 334 called call VBN 335 348 costimulatory costimulatory JJ 349 356 signals signal NNS 356 357 , , , 358 366 mediated mediate VBN 367 369 by by IN 370 375 other other JJ 376 380 cell cell NN 381 388 surface surface NN 389 401 interactions interaction NNS 402 404 or or CC 405 412 soluble soluble JJ 413 422 cytokines cytokine NNS 423 431 produced produce VBN 432 434 by by IN 435 442 antigen antigen NN 443 453 presenting presenting NN 454 459 cells cell NNS 459 460 , , , 461 464 are be VBP 465 469 also also RB 470 478 required require VBN 479 482 for for IN 483 491 complete complete JJ 492 493 T t NN 494 498 cell cell NN 499 509 activation activation NN 509 510 . . . 511 515 High high JJ 516 522 levels level NNS 523 525 of of IN 526 534 cytokine cytokine NN 535 539 gene gene NN 540 550 expression expression NN 551 553 in in IN 554 555 T t NN 556 561 cells cell NNS 562 566 also also RB 567 575 required require VBD 576 580 both both CC 581 584 TCR TCR NNP 585 588 and and CC 589 602 costimulatory costimulatory JJ 603 610 signals signal NNS 610 611 . . . 612 615 The the DT 616 638 granulocyte-macrophage granulocyte-macrophage JJ 639 657 colony-stimulating colony-stimulating JJ 658 664 factor factor NN 665 673 requires require VBZ 674 683 sequences sequence NNS 684 686 in in IN 687 690 the the DT 691 699 promoter promoter NN 700 702 as as RB 703 707 well well RB 708 710 as as IN 711 712 a a DT 713 721 powerful powerful JJ 722 730 enhancer enhancer NN 731 738 located located JJ 739 742 3kb 3kb JJ 743 751 upstream upstream JJ 752 754 to to TO 755 762 respond respond VB 763 765 to to TO 766 774 TCR-like tcr-like JJ 775 782 signals signal NNS 782 783 . . . 784 789 These these DT 790 798 promoter promoter NN 799 802 and and CC 803 811 enhancer enhancer NN 812 819 regions region NNS 820 823 are be VBP 824 830 mainly mainly RB 831 840 activated activate VBN 841 843 by by IN 844 847 the the DT 848 861 transcription transcription NN 862 868 factor factor NN 869 876 nuclear nuclear JJ 877 883 factor factor NN 884 886 of of IN 887 896 activated activate VBN 897 898 T t NN 899 904 cells cell NNS 905 906 ( ( ( 906 910 NFAT NFAT NNP 910 911 ) ) ) 911 912 . . . 913 916 The the DT 917 927 activation activation NN 928 930 of of IN 931 935 NFAT NFAT NNP 936 938 by by IN 939 942 TCR TCR NNP 943 950 signals signal NNS 951 954 has have VBZ 955 959 been be VBN 960 964 well well RB 965 974 described describe VBN 975 978 for for IN 979 992 interleukin-2 interleukin-2 NN 993 994 ( ( ( 994 998 IL-2 il-2 NN 998 999 ) ) ) 1000 1003 and and CC 1004 1008 IL-4 il-4 NN 1009 1013 gene gene NN 1014 1027 transcription transcription NN 1028 1030 in in IN 1031 1032 T t NN 1033 1038 cells cell NNS 1038 1039 . . . 1040 1053 Costimulatory costimulatory JJ 1054 1061 signals signal NNS 1061 1062 , , , 1063 1067 such such JJ 1068 1070 as as IN 1071 1081 activation activation NN 1082 1084 of of IN 1085 1088 the the DT 1089 1093 CD28 cd28 NN 1094 1098 cell cell NN 1099 1106 surface surface NN 1107 1115 molecule molecule NN 1116 1118 on on IN 1119 1120 T t NN 1121 1126 cells cell NNS 1126 1127 , , , 1128 1132 lead lead VBP 1133 1135 to to TO 1136 1146 activation activation NN 1147 1154 through through IN 1155 1156 a a DT 1157 1165 distinct distinct JJ 1166 1172 region region NN 1173 1175 of of IN 1176 1179 the the DT 1180 1202 granulocyte-macrophage granulocyte-macrophage JJ 1203 1221 colony-stimulating colony-stimulating JJ 1222 1228 factor factor NN 1229 1230 ( ( ( 1230 1236 GM-CSF GM-CSF NNP 1236 1237 ) ) ) 1238 1246 promoter promoter NN 1246 1247 . . . 1248 1252 This this DT 1253 1259 region region NN 1260 1262 is be VBZ 1263 1269 termed term VBN 1270 1273 the the DT 1274 1278 CK-1 ck-1 NN 1279 1281 or or CC 1282 1288 CD28RE CD28RE NNP 1289 1292 and and CC 1293 1300 appears appear VBZ 1301 1303 to to TO 1304 1308 bind bind VB 1309 1317 specific specific JJ 1318 1325 members member NNS 1326 1328 of of IN 1329 1332 the the DT 1333 1341 NF-kappa NF-kappa NNP 1342 1343 B B NNP 1344 1350 family family NN 1351 1353 of of IN 1354 1367 transcription transcription NN 1368 1375 factors factor NNS 1375 1376 . . . 1377 1382 Human human JJ 1383 1384 T t NN 1385 1393 leukemia leukemia NN 1394 1399 virus virus NN 1400 1404 type type NN 1405 1406 1 1 CD 1407 1408 ( ( ( 1408 1414 HTLV-1 htlv-1 NN 1414 1415 ) ) ) 1416 1423 infects infect VBZ 1424 1425 T t NN 1426 1431 cells cell NNS 1432 1435 and and CC 1436 1439 can can MD 1440 1444 lead lead VB 1445 1447 to to TO 1448 1456 increase increase VB 1457 1463 GM-CSF GM-CSF NNP 1464 1474 expression expression NN 1474 1475 . . . 1476 1478 We we PRP 1479 1483 have have VBP 1484 1489 found find VBN 1490 1494 that that IN 1495 1498 the the DT 1499 1505 HTLV-1 htlv-1 NN 1506 1520 transactivator transactivator NN 1521 1528 protein protein NN 1528 1529 , , , 1530 1533 tax tax NN 1533 1534 , , , 1535 1539 acts act VBZ 1540 1542 as as IN 1543 1544 a a DT 1545 1558 costimulatory costimulatory JJ 1559 1565 signal signal NN 1566 1569 for for IN 1570 1576 GM-CSF GM-CSF NNP 1577 1580 and and CC 1581 1585 IL-2 il-2 NN 1586 1590 gene gene NN 1591 1604 transcription transcription NN 1604 1605 , , , 1606 1608 in in IN 1609 1613 that that IN 1614 1616 it it PRP 1617 1620 can can MD 1621 1630 cooperate cooperate VB 1631 1635 with with IN 1636 1639 TCR TCR NNP 1640 1647 signals signal NNS 1648 1650 to to TO 1651 1658 mediate mediate VB 1659 1663 high high JJ 1664 1669 level level NN 1670 1674 gene gene NN 1675 1685 expression expression NN 1685 1686 . . . 1687 1690 Tax Tax NNP 1691 1700 activates activate VBZ 1701 1704 the the DT 1705 1711 GM-CSF GM-CSF NNP 1712 1720 promoter promoter NN 1721 1728 through through IN 1729 1732 the the DT 1733 1744 CK-1/CD28RE CK-1/CD28RE NNP 1745 1751 region region NN 1752 1755 and and CC 1756 1760 also also RB 1761 1770 activates activate VBZ 1771 1778 nuclear nuclear JJ 1779 1791 factor-kappa factor-kappa NN 1792 1793 B B NNP 1794 1801 binding bind VBG 1802 1804 to to TO 1805 1809 this this DT 1810 1816 region region NN 1816 1817 . . . 1818 1825 However however RB 1825 1826 , , , 1827 1832 other other JJ 1833 1846 transcription transcription NN 1847 1854 factors factor NNS 1855 1857 or or CC 1858 1870 coactivators coactivator NNS 1871 1873 of of IN 1874 1882 NF-kappa NF-kappa NNP 1883 1884 B B NNP 1885 1888 are be VBP 1889 1897 required require VBN 1898 1901 for for IN 1902 1905 tax tax NN 1906 1916 activation activation NN 1917 1920 but but CC 1921 1926 these these DT 1927 1933 remain remain VBP 1934 1936 to to TO 1937 1939 be be VB 1940 1950 identified identify VBN 1950 1951 . . . 1952 1955 The the DT 1956 1967 CK-1/CD28RE ck-1/cd28re NN 1968 1970 of of IN 1971 1977 GM-CSF GM-CSF NNP 1978 1983 shows show VBZ 1984 1985 a a DT 1986 1990 high high JJ 1991 1997 degree degree NN 1998 2000 of of IN 2001 2011 similarity similarity NN 2012 2014 to to TO 2015 2018 the the DT 2019 2023 IL-2 il-2 NN 2024 2030 CD28RE cd28re NN 2031 2034 and and CC 2035 2038 the the DT 2039 2043 IL-3 il-3 NN 2044 2048 gene gene NN 2049 2053 also also RB 2054 2062 contains contain VBZ 2063 2064 a a DT 2065 2072 related related JJ 2073 2079 region region NN 2079 2080 . . . 2081 2085 This this DT 2086 2097 observation observation NN 2097 2098 , , , 2099 2107 together together RB 2108 2112 with with IN 2113 2116 the the DT 2117 2121 fact fact NN 2122 2126 that that IN 2127 2131 both both CC 2132 2138 GM-CSF GM-CSF NNP 2139 2142 and and CC 2143 2147 IL-2 IL-2 NNP 2148 2155 respond respond VBP 2156 2158 to to TO 2159 2162 TCR TCR NNP 2163 2170 signals signal NNS 2171 2174 via via IN 2175 2179 NFAT NFAT NNP 2179 2180 , , , 2181 2188 implies imply VBZ 2189 2190 a a DT 2191 2195 high high JJ 2196 2202 degree degree NN 2203 2205 of of IN 2206 2218 conservation conservation NN 2219 2221 in in IN 2222 2225 the the DT 2226 2236 regulation regulation NN 2237 2239 of of IN 2240 2248 cytokine cytokine NN 2249 2253 gene gene NN 2254 2264 expression expression NN 2265 2267 in in IN 2268 2269 T t NN 2270 2275 cells cell NNS 2275 2276 . . .