0 16 Characterization characterization NN 17 19 of of IN 20 21 a a DT 22 47 CD43/leukosialin-mediated cd43/leukosialin-mediated JJ 48 55 pathway pathway NN 56 59 for for IN 60 68 inducing induce VBG 69 78 apoptosis apoptosis NN 79 81 in in IN 82 87 human human JJ 88 104 T-lymphoblastoid t-lymphoblastoid JJ 105 110 cells cell NNS 110 111 . . . 113 116 The the DT 117 127 monoclonal monoclonal JJ 128 136 antibody antibody NN 137 138 ( ( ( 138 141 mAb mab NN 141 142 ) ) ) 143 147 J393 j393 NN 148 155 induces induce VBZ 156 165 apoptosis apoptosis NN 166 168 in in IN 169 175 Jurkat Jurkat NNP 176 183 T-cells T-cell NNP 183 184 . . . 185 197 NH2-terminal nh2-terminal JJ 198 203 amino amino NN 204 208 acid acid NN 209 217 sequence sequence NN 218 226 analysis analysis NN 227 237 identified identify VBD 238 241 the the DT 242 249 140-kDa 140-kda JJ 250 257 surface surface NN 258 265 antigen antigen NN 266 269 for for IN 270 273 mAb mab NN 274 278 J393 j393 NN 279 281 as as IN 282 298 CD43/leukosialin CD43/leukosialin NNP 298 299 , , , 300 303 the the DT 304 309 major major JJ 310 327 sialoglycoprotein sialoglycoprotein NN 328 330 of of IN 331 341 leukocytes leukocyte NNS 341 342 . . . 343 348 While while IN 349 355 Jurkat Jurkat NNP 356 361 cells cell NNS 362 374 co-expressed co-expresse VBD 375 378 two two CD 379 387 discrete discrete JJ 388 400 cell-surface cell-surface JJ 401 409 isoforms isoform NNS 410 412 of of IN 413 417 CD43 CD43 NNP 417 418 , , , 419 429 recognized recognize VBN 430 432 by by IN 433 436 mAb mab NN 437 441 J393 j393 NN 442 445 and and CC 446 449 mAb mab NN 450 455 G10-2 g10-2 NN 455 456 , , , 457 469 respectively respectively RB 469 470 , , , 471 475 only only RB 476 485 J393/CD43 j393/cd43 NN 486 494 signaled signal VBD 495 504 apoptosis apoptosis NN 504 505 . . . 506 515 J393/CD43 J393/CD43 NNP 516 519 was be VBD 520 525 found find VBN 526 528 to to TO 529 531 be be VB 532 546 hyposialylated hyposialylate VBN 546 547 , , , 548 555 bearing bear VBG 556 569 predominantly predominantly RB 570 578 O-linked o-linked JJ 579 593 monosaccharide monosaccharide NN 594 601 glycans glycan NNS 601 602 , , , 603 610 whereas whereas IN 611 621 G10-2/CD43 G10-2/CD43 NNP 622 626 bore bore NN 627 634 complex complex NN 635 645 sialylated sialylate VBN 646 652 tetra- tetra- NN 653 656 and and CC 657 671 hexasaccharide hexasaccharide NN 672 678 chains chain NNS 678 679 . . . 680 689 Treatment Treatment NNP 690 694 with with IN 695 702 soluble soluble JJ 702 703 , , , 704 712 bivalent bivalent JJ 713 716 mAb mab NN 717 721 J393 j393 NN 722 728 killed kill VBD 729 734 25-50 25-50 CD 734 735 % % NN 736 738 of of IN 739 742 the the DT 743 747 cell cell NN 748 758 population population NN 758 759 , , , 760 765 while while IN 766 777 concomitant concomitant JJ 778 788 engagement engagement NN 789 791 of of IN 792 798 either either CC 799 802 the the DT 803 810 CD3.TcR cd3.tcr NN 811 818 complex complex NN 819 821 or or CC 822 825 the the DT 826 835 integrins integrin NNS 836 840 CD18 cd18 NN 841 844 and and CC 845 849 CD29 cd29 NN 850 863 significantly significantly RB 864 875 potentiated potentiate VBD 876 880 this this DT 881 887 effect effect NN 887 888 . . . 889 898 Treatment Treatment NNP 899 901 of of IN 902 908 Jurkat Jurkat NNP 909 914 cells cell NNS 915 919 with with IN 920 923 mAb mab NN 924 928 J393 j393 NN 929 936 induced induce VBD 937 945 tyrosine tyrosine NN 946 961 phosphorylation phosphorylation NN 962 964 of of IN 965 973 specific specific JJ 974 981 protein protein NN 982 992 substrates substrate NNS 993 997 that that WDT 998 1007 underwent undergo VBD 1008 1028 hyperphosphorylation hyperphosphorylation NN 1029 1033 upon upon IN 1034 1041 antigen antigen NN 1042 1050 receptor receptor NN 1051 1064 costimulation costimulation NN 1064 1065 . . . 1066 1074 Tyrosine Tyrosine NNP 1075 1081 kinase kinase NNP 1082 1092 inhibition inhibition NN 1093 1095 by by IN 1096 1106 herbimycin herbimycin NN 1107 1108 A a NN 1109 1119 diminished diminish VBD 1120 1138 J393/CD43-mediated j393/cd43-mediated JJ 1139 1148 apoptosis apoptosis NN 1148 1149 , , , 1150 1157 whereas whereas IN 1158 1168 inhibition inhibition NN 1169 1171 of of IN 1172 1187 phosphotyrosine phosphotyrosine NN 1188 1199 phosphatase phosphatase NN 1200 1208 activity activity NN 1209 1211 by by IN 1212 1240 bis(maltolato)oxovanadium-IV bis(maltolato)oxovanadium-iv NN 1241 1249 enhanced enhance VBD 1250 1254 cell cell NN 1255 1260 death death NN 1260 1261 . . . 1262 1268 Signal Signal NNP 1269 1281 transduction transduction NN 1282 1289 through through IN 1290 1298 tyrosine tyrosine NN 1299 1305 kinase kinase NNP 1306 1316 activation activation NN 1317 1320 may may MD 1321 1325 lead lead VB 1326 1328 to to TO 1329 1336 altered altered JJ 1337 1341 gene gene NN 1342 1352 expression expression NN 1352 1353 , , , 1354 1356 as as IN 1357 1366 J393/CD43 j393/cd43 NN 1367 1375 ligation ligation NN 1376 1384 prompted prompt VBD 1385 1394 decreases decrease NNS 1395 1397 in in IN 1398 1401 the the DT 1402 1409 nuclear nuclear JJ 1410 1422 localization localization NN 1423 1425 of of IN 1426 1429 the the DT 1430 1445 transcriptional transcriptional JJ 1446 1456 regulatory regulatory JJ 1457 1464 protein protein NN 1465 1474 NF-kappaB nf-kappab NN 1475 1478 and and CC 1479 1487 proteins protein NNS 1488 1495 binding bind VBG 1496 1499 the the DT 1500 1520 interferon-inducible interferon-inducible JJ 1521 1531 regulatory regulatory JJ 1532 1539 element element NN 1539 1540 . . . 1541 1546 Since since IN 1547 1557 peripheral peripheral JJ 1558 1563 blood blood NN 1564 1577 T-lymphocytes t-lymphocyte NNS 1578 1585 express express VBP 1586 1593 cryptic cryptic JJ 1594 1602 epitopes epitope NNS 1603 1606 for for IN 1607 1610 mAb mab NN 1611 1615 J393 j393 NN 1615 1616 , , , 1617 1622 these these DT 1623 1631 findings finding NNS 1632 1643 demonstrate demonstrate VBP 1644 1647 the the DT 1648 1657 existence existence NN 1658 1660 of of IN 1661 1662 a a DT 1663 1670 tightly tightly RB 1671 1680 regulated regulate VBN 1681 1694 CD43-mediated cd43-mediated JJ 1695 1702 pathway pathway NN 1703 1706 for for IN 1707 1715 inducing induce VBG 1716 1725 apoptosis apoptosis NN 1726 1728 in in IN 1729 1734 human human JJ 1735 1741 T-cell t-cell NN 1742 1750 lineages lineage NNS 1750 1751 . . .