0 4 IL-2 il-2 NN 5 9 gene gene NN 10 20 expression expression NN 21 24 and and CC 25 33 NF-kappa NF-kappa NNP 34 35 B B NNP 36 46 activation activation NN 47 54 through through IN 55 59 CD28 cd28 NN 60 68 requires require VBZ 69 77 reactive reactive JJ 78 84 oxygen oxygen NN 85 95 production production NN 96 98 by by IN 99 113 5-lipoxygenase 5-lipoxygenase NN 113 114 . . . 116 126 Activation Activation NNP 127 129 of of IN 130 133 the the DT 134 138 CD28 cd28 NN 139 146 surface surface NN 147 155 receptor receptor NN 156 164 provides provide VBZ 165 166 a a DT 167 172 major major JJ 173 186 costimulatory costimulatory JJ 187 193 signal signal NN 194 197 for for IN 198 199 T t NN 200 204 cell cell NN 205 215 activation activation NN 216 225 resulting result VBG 226 228 in in IN 229 237 enhanced enhance VBN 238 248 production production NN 249 251 of of IN 252 265 interleukin-2 interleukin-2 NN 266 267 ( ( ( 267 271 IL-2 il-2 NN 271 272 ) ) ) 273 276 and and CC 277 281 cell cell NN 282 295 proliferation proliferation NN 295 296 . . . 297 299 In in IN 300 307 primary primary JJ 308 309 T t NN 310 321 lymphocytes lymphocyte NNS 322 324 we we PRP 325 329 show show VBP 330 334 that that IN 335 339 CD28 cd28 NN 340 348 ligation ligation NN 349 354 leads lead VBZ 355 357 to to TO 358 361 the the DT 362 367 rapid rapid JJ 368 381 intracellular intracellular JJ 382 391 formation formation NN 392 394 of of IN 395 403 reactive reactive JJ 404 410 oxygen oxygen NN 411 424 intermediates intermediate NNS 425 426 ( ( ( 426 430 ROIs ROI NNP 430 431 ) ) ) 432 437 which which WDT 438 441 are be VBP 442 450 required require VBN 451 454 for for IN 455 468 CD28-mediated cd28-mediated JJ 469 479 activation activation NN 480 482 of of IN 483 486 the the DT 487 495 NF-kappa NF-kappa NNP 496 513 B/CD28-responsive b/cd28-responsive JJ 514 521 complex complex NN 522 525 and and CC 526 530 IL-2 il-2 NN 531 541 expression expression NN 541 542 . . . 543 554 Delineation Delineation NNP 555 557 of of IN 558 561 the the DT 562 566 CD28 cd28 NN 567 576 signaling signaling NN 577 584 cascade cascade NN 585 588 was be VBD 589 594 found find VBN 595 597 to to TO 598 605 involve involve VB 606 613 protein protein NN 614 622 tyrosine tyrosine NN 623 629 kinase kinase NNP 630 638 activity activity NN 638 639 , , , 640 648 followed follow VBN 649 651 by by IN 652 655 the the DT 656 666 activation activation NN 667 669 of of IN 670 683 phospholipase phospholipase NN 684 686 A2 a2 NN 687 690 and and CC 691 705 5-lipoxygenase 5-lipoxygenase NN 705 706 . . . 707 710 Our our PRP$ 711 715 data datum NNS 716 723 suggest suggest VBP 724 728 that that IN 729 741 lipoxygenase lipoxygenase NN 742 753 metabolites metabolite NNS 754 762 activate activate VBP 763 766 ROI ROI NNP 767 776 formation formation NN 777 782 which which WDT 783 787 then then RB 788 794 induce induce VBP 795 799 IL-2 il-2 NN 800 810 expression expression NN 811 814 via via IN 815 823 NF-kappa NF-kappa NNP 824 825 B B NNP 826 836 activation activation NN 836 837 . . . 838 843 These these DT 844 852 findings finding NNS 853 859 should should MD 860 862 be be VB 863 869 useful useful JJ 870 873 for for IN 874 885 therapeutic therapeutic JJ 886 896 strategies strategy NNS 897 900 and and CC 901 904 the the DT 905 916 development development NN 917 919 of of IN 920 938 immunosuppressants immunosuppressant NNS 939 948 targeting target VBG 949 952 the the DT 953 957 CD28 cd28 NN 958 971 costimulatory costimulatory JJ 972 979 pathway pathway NN 979 980 . . .