0 5 Jeg-3 jeg-3 NN 6 11 human human JJ 12 35 choriocarcinoma-induced choriocarcinoma-induced JJ 36 53 immunosuppression immunosuppression NN 53 54 : : : 55 69 downregulation downregulation NN 70 72 of of IN 73 86 interleukin-2 interleukin-2 NN 86 87 , , , 88 101 interleukin-2 interleukin-2 NN 102 110 receptor receptor NN 111 122 alpha-chain alpha-chain NN 122 123 , , , 124 127 and and CC 128 131 its its PRP$ 132 140 Jak/Stat jak/stat NN 141 150 signaling signaling NN 151 158 pathway pathway NN 158 159 . . . 161 168 PROBLEM problem NN 168 169 : : : 170 173 The the DT 174 184 mechanisms mechanism NNS 185 187 of of IN 188 191 the the DT 192 209 immunosuppressive immunosuppressive JJ 210 213 and and CC 214 240 immunosuppression-inducing immunosuppression-inducing JJ 241 251 capacities capacity NNS 252 254 of of IN 255 260 Jeg-3 jeg-3 NN 261 266 human human JJ 267 282 choriocarcinoma choriocarcinoma NN 283 287 cell cell NN 288 292 line line NN 293 305 supernatants supernatant NNS 306 307 ( ( ( 307 311 HCSs HCS NNPS 311 312 ) ) ) 313 316 are be VBP 317 320 not not RB 321 324 yet yet RB 325 335 completely completely RB 336 347 understood. understood. VB 348 351 The the DT 352 361 influence influence NN 362 364 on on IN 365 376 interleukin interleukin NN 377 378 ( ( ( 378 383 IL)-2 il)-2 NN 383 384 , , , 385 389 IL-4 il-4 NN 390 393 and and CC 394 404 interferon interferon NN 405 406 ( ( ( 406 416 IFN)-gamma IFN)-gamma NNP 417 427 production production NN 427 428 ; ; : 429 433 IL-2 il-2 NN 434 442 receptor receptor NN 443 444 ( ( ( 444 449 IL-2R IL-2R NNP 449 450 ) ) ) 451 457 alpha- alpha- NN 457 458 , , , 459 464 beta- beta- NN 464 465 , , , 466 469 and and CC 470 481 gamma-chain gamma-chain NN 481 482 ; ; : 483 486 and and CC 487 490 the the DT 491 500 signaling signaling NN 501 508 pathway pathway NN 509 518 molecules molecule NNS 519 524 Janus Janus NNP 525 531 kinase kinase NNP 532 533 ( ( ( 533 538 Jak)1 Jak)1 NNP 538 539 , , , 540 544 Jak3 Jak3 NNP 544 545 , , , 546 552 signal signal NN 553 564 transducers transducer NNS 565 568 and and CC 569 579 activators activator NNS 580 582 of of IN 583 596 transcription transcription NN 597 598 ( ( ( 598 604 Stat)1 Stat)1 NNP 604 605 , , , 606 611 Stat3 Stat3 NNP 611 612 , , , 613 616 and and CC 617 622 Stat5 Stat5 NNP 623 629 should should MD 630 632 be be VB 633 645 investigated investigate VBN 645 646 . . . 647 653 METHOD method NN 654 656 OF of IN 657 662 STUDY STUDY NNP 662 663 : : : 664 667 For for IN 668 678 assessment assessment NN 679 681 of of IN 682 684 IL IL NNP 685 695 production production NN 695 696 , , , 697 702 whole whole JJ 703 713 peripheral peripheral JJ 714 720 venous venous JJ 721 726 blood blood NN 727 731 from from IN 732 739 healthy healthy JJ 740 746 donors donor NNS 747 750 was be VBD 751 761 stimulated stimulate VBN 762 766 with with IN 767 792 phorbol-myristate-acetate phorbol-myristate-acetate NN 793 796 and and CC 797 807 ionomycine ionomycine NN 807 808 . . . 809 818 Secretion Secretion NNP 819 821 of of IN 822 825 ILs IL NNP 826 829 was be VBD 830 837 blocked block VBN 838 842 with with IN 843 852 monensine monensine NN 852 853 . . . 854 867 Intracellular intracellular JJ 868 871 ILs IL NNP 872 876 were be VBD 877 885 analyzed analyze VBN 886 888 by by IN 889 893 flow flow NN 894 903 cytometry cytometry NN 903 904 . . . 905 908 For for IN 909 914 IL-2R IL-2R NNP 915 918 and and CC 919 928 signaling signaling NN 929 936 pathway pathway NN 937 945 molecule molecule NN 946 954 analysis analysis NN 954 955 , , , 956 966 peripheral peripheral JJ 967 972 blood blood NN 973 984 lymphocytes lymphocyte NNS 985 989 were be VBD 990 1000 stimulated stimulate VBN 1001 1005 with with IN 1006 1024 phytohemagglutinin phytohemagglutinin NN 1025 1026 ( ( ( 1026 1029 PHA PHA NNP 1029 1030 ) ) ) 1030 1031 . . . 1032 1037 IL-2R IL-2R NNP 1038 1044 chains chain NNS 1045 1049 were be VBD 1050 1058 measured measure VBN 1059 1061 by by IN 1062 1066 flow flow NN 1067 1076 cytometry cytometry NN 1076 1077 , , , 1078 1081 and and CC 1082 1092 Jaks/Stats jaks/stat NNS 1093 1095 by by IN 1096 1102 sodium sodium NN 1103 1110 dodecyl dodecyl NN 1111 1118 sulfate sulfate NN 1119 1133 polyacrylamide polyacrylamide NN 1134 1137 gel gel NN 1138 1153 electrophoresis electrophoresis NN 1154 1155 ( ( ( 1155 1163 SDS-PAGE sds-page NN 1163 1164 ) ) ) 1165 1168 and and CC 1169 1176 Western western NN 1177 1181 blot blot NN 1181 1182 . . . 1183 1190 RESULTS results NNS 1190 1191 : : : 1192 1217 Phorbol-myristate-acetate Phorbol-myristate-acetate NNP 1218 1221 and and CC 1222 1232 ionomycine ionomycine NN 1233 1241 strongly strongly RB 1242 1250 increase increase VBP 1251 1254 the the DT 1255 1266 percent-age percent-age NN 1267 1269 of of IN 1270 1275 IL-2+ il-2+ JJ 1276 1281 cells cell NNS 1281 1282 ; ; : 1283 1285 an an DT 1286 1296 additional additional JJ 1297 1299 50 50 CD 1299 1300 % % NN 1301 1305 HCSs hcs NNS 1306 1319 significantly significantly RB 1320 1330 suppresses suppress VBZ 1331 1334 the the DT 1335 1345 percentage percentage NN 1346 1348 to to TO 1348 1349 , , , 1350 1352 or or CC 1353 1358 below below IN 1359 1362 the the DT 1363 1368 level level NN 1369 1371 of of IN 1372 1384 unstimulated unstimulated JJ 1385 1390 cells cell NNS 1390 1391 . . . 1392 1401 IFN-gamma IFN-gamma NNP 1402 1412 production production NN 1413 1415 is be VBZ 1416 1424 strongly strongly RB 1425 1434 decreased decrease VBN 1435 1437 by by IN 1438 1442 HCSs hcs NNS 1443 1445 in in IN 1446 1450 some some DT 1451 1456 cases case NNS 1456 1457 , , , 1458 1461 but but CC 1462 1465 not not RB 1466 1468 in in IN 1469 1475 others other NNS 1475 1476 . . . 1477 1480 PHA PHA NNP 1481 1491 stimulates stimulate VBZ 1492 1497 IL-2R il-2r NN 1498 1504 alpha- alpha- NN 1504 1505 , , , 1506 1511 beta- beta- NN 1511 1512 , , , 1513 1516 and and CC 1517 1528 gamma-chain gamma-chain NN 1529 1539 expression expression NN 1540 1543 and and CC 1544 1549 their their PRP$ 1550 1559 signaling signaling NN 1560 1567 pathway pathway NN 1568 1577 molecules molecule NNS 1578 1582 Jak1 jak1 NN 1582 1583 , , , 1584 1588 Jak3 Jak3 NNP 1588 1589 , , , 1590 1595 Stat1 Stat1 NNP 1595 1596 , , , 1597 1602 Stat3 Stat3 NNP 1602 1603 , , , 1604 1607 and and CC 1608 1613 Stat5 Stat5 NNP 1613 1614 . . . 1615 1617 50 50 CD 1617 1618 % % NN 1619 1622 HCS hcs NN 1623 1636 downregulates downregulate VBZ 1637 1640 the the DT 1641 1652 alpha-chain alpha-chain NN 1653 1656 and and CC 1657 1665 slightly slightly RB 1666 1677 upregulates upregulate VBZ 1678 1681 the the DT 1682 1692 beta-chain beta-chain NN 1692 1693 . . . 1694 1698 Jak1 Jak1 NNP 1698 1699 , , , 1700 1704 Jak3 Jak3 NNP 1704 1705 , , , 1706 1711 Stat1 Stat1 NNP 1711 1712 , , , 1713 1718 Stat3 Stat3 NNP 1718 1719 , , , 1720 1723 and and CC 1724 1729 Stat5 Stat5 NNP 1730 1740 expression expression NN 1741 1743 is be VBZ 1744 1754 suppressed suppress VBN 1755 1768 approximately approximately RB 1769 1771 to to TO 1771 1772 , , , 1773 1775 or or CC 1776 1781 below below IN 1782 1785 the the DT 1786 1791 level level NN 1792 1794 of of IN 1795 1807 unstimulated unstimulated JJ 1808 1813 cells cell NNS 1813 1814 . . . 1815 1826 CONCLUSIONS conclusions NNS 1826 1827 : : : 1828 1831 HCS HCS NNP 1832 1842 forcefully forcefully RB 1843 1849 blocks block VBZ 1850 1853 the the DT 1854 1864 production production NN 1865 1867 of of IN 1868 1872 IL-2 il-2 NN 1872 1873 ; ; : 1874 1877 the the DT 1878 1883 IL-2R IL-2R NNP 1884 1895 alpha-chain alpha-chain NN 1895 1896 ; ; : 1897 1900 and and CC 1901 1905 Jak1 Jak1 NNP 1905 1906 , , , 1907 1911 Jak3 Jak3 NNP 1911 1912 , , , 1913 1918 Stat1 Stat1 NNP 1918 1919 , , , 1920 1925 Stat3 Stat3 NNP 1925 1926 , , , 1927 1930 and and CC 1931 1936 Stat5 Stat5 NNP 1937 1947 expression expression NN 1947 1948 . . . 1949 1952 The the DT 1953 1961 observed observe VBN 1962 1971 phenomena phenomenon NNS 1972 1977 might might MD 1978 1980 be be VB 1981 1987 caused cause VBN 1988 1990 by by IN 1991 2005 downregulation downregulation NN 2006 2008 of of IN 2009 2011 an an DT 2012 2017 IL-2R IL-2R NNP 2018 2028 regulation regulation NN 2029 2033 gene gene NN 2033 2034 , , , 2035 2038 and and CC 2039 2044 might might MD 2045 2049 play play VB 2050 2051 a a DT 2052 2055 key key JJ 2056 2060 role role NN 2061 2063 in in IN 2064 2067 the the DT 2068 2077 expansion expansion NN 2078 2080 of of IN 2081 2096 choriocarcinoma choriocarcinoma NN 2096 2097 , , , 2098 2101 and and CC 2102 2110 possibly possibly RB 2111 2113 in in IN 2114 2117 the the DT 2118 2126 survival survival NN 2127 2129 of of IN 2130 2133 the the DT 2134 2139 fetal fetal JJ 2140 2149 allograft allograft NN 2149 2150 . . .