0 23 Dimethyldithiocarbamate Dimethyldithiocarbamate NNP 24 32 inhibits inhibit VBZ 33 35 in in FW 36 41 vitro vitro FW 42 52 activation activation NN 53 55 of of IN 56 63 primary primary JJ 64 69 human human JJ 70 74 CD4+ cd4+ JJ 75 76 T t NN 77 88 lymphocytes lymphocyte NNS 88 89 . . . 91 107 Dithiocarbamates Dithiocarbamate NNP 108 109 ( ( ( 109 112 DTC DTC NNP 112 113 ) ) ) 113 114 , , , 115 116 a a DT 117 124 diverse diverse JJ 125 130 group group NN 131 133 of of IN 134 144 industrial industrial JJ 145 148 and and CC 149 160 therapeutic therapeutic JJ 161 170 chemicals chemical NNS 170 171 , , , 172 176 have have VBP 177 181 been be VBN 182 190 reported report VBN 191 193 to to TO 194 201 inhibit inhibit VB 201 202 , , , 203 210 enhance enhance VB 211 213 or or CC 214 218 have have VB 219 221 no no DT 222 228 effect effect NN 229 231 on on IN 232 235 the the DT 236 242 immune immune JJ 243 249 system system NN 249 250 . . . 251 256 These these DT 257 265 apparent apparent JJ 266 281 inconsistencies inconsistency NNS 282 289 reflect reflect VBP 290 293 the the DT 294 304 complexity complexity NN 305 307 of of IN 308 311 the the DT 312 316 DTCs DTC NNP 317 327 biological biological JJ 328 338 activities activity NNS 339 342 and and CC 343 346 are be VBP 347 355 probably probably RB 356 359 due due JJ 360 362 in in IN 363 367 part part NN 368 370 to to TO 371 382 differences difference NNS 383 385 in in IN 386 390 dose dose NN 390 391 , , , 392 397 route route NN 398 400 of of IN 401 409 exposure exposure NN 409 410 , , , 411 417 animal animal NN 418 425 species specie NNS 426 430 used use VBN 431 437 and/or and/or CC 438 446 specific specific JJ 447 455 compound compound NN 456 462 tested test VBN 462 463 . . . 464 467 The the DT 468 475 studies study NNS 476 485 described describe VBN 486 492 herein herein RB 493 497 were be VBD 498 508 undertaken undertake VBN 509 511 to to TO 512 523 investigate investigate VB 524 527 the the DT 528 542 immunotoxicity immunotoxicity NN 543 545 of of IN 546 549 one one CD 550 556 member member NN 557 559 of of IN 560 564 this this DT 565 571 family family NN 571 572 , , , 573 596 dimethyldithiocarbamate dimethyldithiocarbamate NN 597 598 ( ( ( 598 603 DMDTC DMDTC NNP 603 604 ) ) ) 604 605 . . . 606 608 We we PRP 609 620 demonstrate demonstrate VBP 621 625 that that IN 626 633 0.1-0.5 0.1-0.5 CD 634 640 microM microM NNP 641 646 DMDTC DMDTC NNP 647 655 inhibits inhibit VBZ 656 673 TNF-alpha-induced tnf-alpha-induced JJ 674 684 activation activation NN 685 687 of of IN 688 697 NF-kappaB NF-kappaB NNP 698 700 in in IN 701 708 primary primary JJ 709 714 human human JJ 715 719 CD4+ cd4+ JJ 720 721 T t NN 722 727 cells cell NNS 727 728 . . . 729 733 This this DT 734 744 inhibition inhibition NN 745 747 is be VBZ 748 751 not not RB 752 763 accompanied accompany VBN 764 766 by by IN 767 768 a a DT 769 773 loss loss NN 774 776 in in IN 777 786 viability viability NN 786 787 , , , 788 791 and and CC 792 805 DMDTC-treated dmdtc-treated JJ 806 807 T t NN 808 813 cells cell NNS 814 820 retain retain VBP 821 826 other other JJ 827 833 active active JJ 834 843 signaling signaling NN 844 852 pathways pathway NNS 853 863 throughout throughout IN 864 867 the the DT 868 876 exposure exposure NN 877 885 duration duration NN 885 886 . . . 887 890 The the DT 891 901 inhibition inhibition NN 902 904 of of IN 905 914 NF-kappaB NF-kappaB NNP 915 917 is be VBZ 918 928 apparently apparently RB 929 938 permanent permanent JJ 939 941 as as IN 942 955 DMDTC-treated dmdtc-treated JJ 956 957 T t NN 958 963 cells cell NNS 964 967 did do VBD 968 971 not not RB 972 978 regain regain VB 979 985 normal normal JJ 986 995 TNF-alpha TNF-alpha NNP 996 1006 activation activation NN 1006 1007 , , , 1008 1012 even even RB 1013 1018 after after IN 1019 1021 72 72 CD 1022 1023 h h NN 1024 1026 in in IN 1027 1034 culture culture NN 1034 1035 . . . 1036 1041 DMDTC DMDTC NNP 1042 1046 does do VBZ 1047 1050 not not RB 1051 1057 appear appear VB 1058 1060 to to TO 1061 1066 alter alter VB 1067 1076 NF-kappaB NF-kappaB NNP 1077 1085 directly directly RB 1086 1088 as as IN 1089 1103 pre-incubation pre-incubation NN 1104 1106 of of IN 1107 1114 nuclear nuclear JJ 1115 1123 extracts extract NNS 1124 1128 with with IN 1129 1134 DMDTC DMDTC NNP 1135 1139 does do VBZ 1140 1143 not not RB 1144 1152 diminish diminish VB 1153 1160 binding binding NN 1161 1169 activity activity NN 1170 1172 of of IN 1173 1177 this this DT 1178 1185 protein protein NN 1185 1186 . . . 1187 1189 We we PRP 1190 1197 further further RB 1198 1209 demonstrate demonstrate VBP 1210 1214 that that IN 1215 1222 0.1-0.5 0.1-0.5 CD 1223 1229 microM microM NNP 1230 1235 DMDTC DMDTC NNP 1236 1244 inhibits inhibit VBZ 1245 1258 intracellular intracellular JJ 1259 1263 IL-2 il-2 NN 1264 1274 production production NN 1275 1278 and and CC 1279 1288 decreases decrease VBZ 1289 1296 surface surface NN 1297 1307 expression expression NN 1308 1310 of of IN 1311 1315 CD25 cd25 NN 1316 1317 ( ( ( 1317 1320 the the DT 1321 1326 alpha alpha NN 1327 1334 subunit subunit NN 1335 1337 of of IN 1338 1341 the the DT 1342 1346 IL-2 il-2 NN 1347 1355 receptor receptor NN 1355 1356 ) ) ) 1357 1359 in in IN 1360 1361 T t NN 1362 1367 cells cell NNS 1368 1378 stimulated stimulate VBN 1379 1383 with with IN 1384 1391 phorbol phorbol NN 1392 1397 ester ester NN 1397 1398 . . . 1399 1404 These these DT 1405 1409 data datum NNS 1410 1421 demonstrate demonstrate VBP 1422 1426 that that IN 1427 1432 DMDTC DMDTC NNP 1433 1435 is be VBZ 1436 1437 a a DT 1438 1444 potent potent JJ 1445 1462 immunosuppressive immunosuppressive JJ 1463 1471 compound compound NN 1472 1474 in in FW 1475 1480 vitro vitro FW 1480 1481 . . .