0 4 Mice mouse NNS 5 14 deficient deficient JJ 15 18 for for IN 19 22 the the DT 23 25 55 55 CD 26 28 kd kd NN 29 34 tumor tumor NN 35 43 necrosis necrosis NN 44 50 factor factor NN 51 59 receptor receptor NN 60 63 are be VBP 64 73 resistant resistant JJ 74 76 to to TO 77 86 endotoxic endotoxic JJ 87 92 shock shock NN 92 93 , , , 94 97 yet yet RB 98 105 succumb succumb VBP 106 108 to to TO 109 111 L. L. NNP 112 125 monocytogenes monocytogene NNS 126 135 infection infection NN 135 136 . . . 138 141 The the DT 142 150 multiple multiple JJ 151 161 biological biological JJ 162 172 activities activity NNS 173 175 of of IN 176 181 tumor tumor NN 182 190 necrosis necrosis NN 191 197 factor factor NN 198 199 ( ( ( 199 202 TNF TNF NNP 202 203 ) ) ) 204 207 are be VBP 208 216 mediated mediate VBN 217 219 by by IN 220 223 two two CD 224 232 distinct distinct JJ 233 237 cell cell NN 238 245 surface surface NN 246 255 receptors receptor NNS 256 258 of of IN 259 261 55 55 CD 262 264 kd kd NN 265 266 ( ( ( 266 273 TNFRp55 TNFRp55 NNP 273 274 ) ) ) 275 278 and and CC 279 281 75 75 CD 282 284 kd kd NN 285 286 ( ( ( 286 293 TNFRp75 TNFRp75 NNP 293 294 ) ) ) 294 295 . . . 296 301 Using use VBG 302 306 gene gene NN 307 316 targeting targeting NN 316 317 , , , 318 320 we we PRP 321 330 generated generate VBD 331 332 a a DT 333 350 TNFRp55-deficient tnfrp55-deficient JJ 351 356 mouse mouse NN 357 363 strain strain NN 363 364 . . . 365 370 Cells cell NNS 371 375 from from IN 376 392 TNFRp55-/-mutant tnfrp55-/-mutant JJ 393 397 mice mouse NNS 398 402 lack lack VBP 403 413 expression expression NN 414 416 of of IN 417 424 TNFRp55 tnfrp55 NN 425 428 but but CC 429 436 display display VBP 437 443 normal normal JJ 444 451 numbers number NNS 452 454 of of IN 455 459 high high JJ 460 468 affinity affinity NN 469 476 TNFRp75 tnfrp75 NN 477 486 molecules molecule NNS 486 487 . . . 488 497 Thymocyte Thymocyte NNP 498 509 development development NN 510 513 and and CC 514 524 lymphocyte lymphocyte NN 525 536 populations population NNS 537 540 are be VBP 541 550 unaltered unaltered JJ 550 551 , , , 552 555 and and CC 556 562 clonal clonal JJ 563 571 deletion deletion NN 572 574 of of IN 575 586 potentially potentially RB 587 600 self-reactive self-reactive JJ 601 602 T t NN 603 608 cells cell NNS 609 611 is be VBZ 612 615 not not RB 616 624 impaired impaired JJ 624 625 . . . 626 633 However however RB 633 634 , , , 635 638 TNF tnf NN 639 648 signaling signaling NN 649 651 is be VBZ 652 659 largely largely RB 660 669 abolished abolish VBN 669 670 , , , 671 673 as as IN 674 680 judged judge VBN 681 683 by by IN 684 687 the the DT 688 695 failure failure NN 696 698 of of IN 699 702 TNF TNF NNP 703 705 to to TO 706 712 induce induce VB 713 721 NF-kappa NF-kappa NNP 722 723 B B NNP 724 726 in in IN 727 728 T t NN 729 740 lymphocytes lymphocyte NNS 741 745 from from IN 746 763 TNFRp55-deficient tnfrp55-deficient JJ 764 768 mice mouse NNS 768 769 . . . 770 773 The the DT 774 778 loss loss NN 779 781 of of IN 782 789 TNFRp55 TNFRp55 NNP 790 798 function function NN 799 806 renders render VBZ 807 811 mice mouse NNS 812 821 resistant resistant JJ 822 824 to to TO 825 831 lethal lethal JJ 832 839 dosages dosage NNS 840 842 of of IN 843 849 either either CC 850 869 lipopolysaccharides lipopolysaccharide NNS 870 872 or or CC 873 875 S. s. FW 876 882 aureus aureus FW 883 894 enterotoxin enterotoxin NN 895 897 B. B. NNP 898 900 In in IN 901 909 contrast contrast NN 909 910 , , , 911 928 TNFRp55-deficient tnfrp55-deficient JJ 929 933 mice mouse NNS 934 937 are be VBP 938 946 severely severely RB 947 955 impaired impaired JJ 956 958 to to TO 959 964 clear clear VB 965 967 L. L. NNP 968 981 monocytogenes monocytogene NNS 982 985 and and CC 986 993 readily readily RB 994 1001 succumb succumb VBP 1002 1004 to to TO 1005 1014 infection infection NN 1014 1015 . . . 1016 1020 Thus thus RB 1020 1021 , , , 1022 1025 the the DT 1026 1028 55 55 CD 1029 1031 kd kd NN 1032 1036 TNFR tnfr NN 1037 1042 plays play VBZ 1043 1044 a a DT 1045 1053 decisive decisive JJ 1054 1058 role role NN 1059 1061 in in IN 1062 1065 the the DT 1066 1070 host host NN 1070 1072 ’s 's POS 1073 1080 defense defense NN 1081 1088 against against IN 1089 1103 microorganisms microorganism NNS 1104 1107 and and CC 1108 1113 their their PRP$ 1114 1124 pathogenic pathogenic JJ 1125 1132 factors factor NNS 1132 1133 . . .