0 10 Signalling signalling NN 11 14 via via IN 15 19 CD28 cd28 NN 20 22 of of IN 23 28 human human JJ 29 34 naive naive JJ 35 43 neonatal neonatal JJ 44 45 T t NN 46 57 lymphocytes lymphocyte NNS 57 58 . . . 60 69 Accessory accessory JJ 70 79 molecules molecule NNS 80 84 play play VBP 85 86 a a DT 87 94 crucial crucial JJ 95 99 role role NN 100 102 in in IN 103 106 the the DT 107 118 development development NN 119 121 of of IN 122 125 the the DT 126 127 T t NN 128 132 cell cell NN 133 141 response response NN 142 144 to to TO 145 154 antigenic antigenic JJ 155 164 challenge challenge NN 164 165 . . . 166 168 We we PRP 169 173 have have VBP 174 182 examined examine VBN 183 186 the the DT 187 191 role role NN 192 194 of of IN 195 199 CD28 cd28 NN 200 202 in in IN 203 213 modulating modulate VBG 214 217 the the DT 218 219 ‘ ` `` 219 224 naive naive JJ 224 225 ’ ' '' 226 234 neonatal neonatal JJ 235 236 T t NN 237 241 cell cell NN 242 250 response response NN 251 253 to to TO 254 271 anti-CD2-mediated anti-cd2-mediated JJ 272 282 activation activation NN 282 283 . . . 284 286 To to TO 287 294 compare compare VB 295 298 the the DT 299 303 role role NN 304 306 of of IN 307 311 CD28 cd28 NN 311 312 , , , 313 321 neonatal neonatal JJ 322 325 and and CC 326 331 adult adult JJ 332 333 T t NN 334 339 cells cell NNS 340 344 were be VBD 345 355 stimulated stimulate VBN 356 360 with with IN 361 362 a a DT 363 367 pair pair NN 368 370 of of IN 371 380 mitogenic mitogenic JJ 381 389 anti-CD2 anti-cd2 JJ 390 400 antibodies antibody NNS 401 403 in in IN 404 407 the the DT 408 416 presence presence NN 417 419 or or CC 420 427 absence absence NN 428 430 of of IN 431 440 anti-CD28 anti-cd28 JJ 441 445 MoAb MoAb NNP 445 446 . . . 447 451 With with IN 452 460 anti-CD2 anti-cd2 NN 461 466 alone alone RB 466 467 , , , 468 476 neonatal neonatal JJ 477 478 T t NN 479 484 cells cell NNS 485 497 proliferated proliferate VBD 498 506 slightly slightly RB 507 510 but but CC 511 519 produced produce VBD 520 522 no no DT 523 533 detectable detectable JJ 534 538 IL-2 il-2 NN 538 539 , , , 540 547 whereas whereas IN 548 553 adult adult JJ 554 555 T t NN 556 561 cells cell NNS 562 574 proliferated proliferate VBD 575 585 vigorously vigorously RB 585 586 , , , 587 591 with with IN 592 603 significant significant JJ 604 608 IL-2 il-2 NN 609 619 production production NN 619 620 . . . 621 634 Costimulation costimulation NN 635 639 with with IN 640 649 anti-CD28 anti-cd28 JJ 650 654 MoAb MoAb NNP 655 662 greatly greatly RB 663 671 enhanced enhance VBD 672 675 the the DT 676 689 proliferative proliferative JJ 690 698 response response NN 699 701 of of IN 702 710 neonatal neonatal JJ 711 712 T t NN 713 718 cells cell NNS 719 721 to to TO 722 728 levels level NNS 729 739 equivalent equivalent JJ 740 742 to to TO 743 748 those those DT 749 751 of of IN 752 757 adult adult JJ 758 759 T t NN 760 765 cells cell NNS 765 766 , , , 767 774 whereas whereas IN 775 780 adult adult JJ 781 782 T t NN 783 788 cells cell NNS 789 795 showed show VBD 796 800 only only RB 801 807 slight slight JJ 808 817 increases increase NNS 817 818 . . . 819 827 Although although IN 828 832 IL-2 il-2 NN 833 842 secretion secretion NN 843 846 was be VBD 847 856 increased increase VBN 857 859 in in IN 860 863 the the DT 864 872 presence presence NN 873 875 of of IN 876 885 anti-CD28 anti-cd28 JJ 886 890 MoAb MoAb NNP 890 891 , , , 892 900 neonatal neonatal JJ 901 902 T t NN 903 907 cell cell NN 908 912 IL-2 il-2 NN 913 923 production production NN 924 932 remained remain VBD 933 938 lower low JJR 939 943 than than IN 944 946 in in IN 947 953 adults adult NNS 953 954 . . . 955 957 In in IN 958 966 contrast contrast NN 966 967 , , , 968 979 enhancement enhancement NN 980 982 of of IN 983 987 IL-2 il-2 NN 988 992 mRNA mrna NN 993 1003 expression expression NN 1004 1006 in in IN 1007 1015 neonates neonate NNS 1016 1019 was be VBD 1020 1027 similar similar JJ 1028 1030 to to TO 1031 1036 adult adult JJ 1037 1043 levels level NNS 1043 1044 . . . 1045 1054 Anti-CD28 anti-cd28 JJ 1055 1059 MoAb MoAb NNP 1060 1073 costimulation costimulation NN 1074 1083 increased increase VBD 1084 1086 NF NF NNP 1087 1092 kappa kappa NN 1093 1094 B B NNP 1095 1101 levels level NNS 1102 1104 in in IN 1105 1113 neonates neonate NNS 1113 1114 , , , 1115 1121 albeit albeit IN 1122 1124 to to TO 1125 1131 levels level NNS 1132 1137 lower low JJR 1138 1142 than than IN 1143 1147 that that DT 1148 1150 of of IN 1151 1157 adults adult NNS 1157 1158 . . . 1159 1162 The the DT 1163 1171 cellular cellular JJ 1172 1181 mechanism mechanism NN 1182 1191 governing govern VBG 1192 1195 the the DT 1196 1206 diminished diminish VBN 1207 1220 proliferative proliferative JJ 1221 1229 response response NN 1230 1232 of of IN 1233 1241 neonatal neonatal JJ 1242 1243 T t NN 1244 1255 lymphocytes lymphocyte NNS 1256 1258 to to TO 1259 1267 anti-CD2 anti-cd2 NN 1268 1271 may may MD 1272 1281 therefore therefore RB 1282 1284 be be VB 1285 1288 due due JJ 1289 1291 to to TO 1292 1301 decreased decrease VBN 1302 1304 NF NF NNP 1305 1310 kappa kappa NN 1311 1312 B B NNP 1313 1322 induction induction NN 1322 1323 , , , 1324 1331 reduced reduce VBD 1332 1336 IL-2 il-2 NN 1337 1341 mRNA mrna NN 1342 1352 expression expression NN 1353 1356 and and CC 1357 1366 deficient deficient JJ 1367 1371 IL-2 il-2 NN 1372 1382 production production NN 1382 1383 . . . 1384 1392 Although although IN 1393 1402 anti-CD28 anti-cd28 JJ 1403 1407 MoAb MoAb NNP 1408 1421 costimulation costimulation NN 1422 1430 enhances enhance VBZ 1431 1434 all all DT 1435 1437 of of IN 1438 1441 the the DT 1442 1447 above above JJ 1448 1455 signals signal NNS 1455 1456 , , , 1457 1459 NF NF NNP 1460 1465 kappa kappa NN 1466 1467 B B NNP 1468 1471 and and CC 1472 1476 IL-2 il-2 NN 1477 1483 levels level NNS 1484 1490 remain remain VBP 1491 1496 lower low JJR 1497 1501 than than IN 1502 1504 in in IN 1505 1511 adults adult NNS 1511 1512 , , , 1513 1523 suggesting suggest VBG 1524 1527 the the DT 1528 1532 need need NN 1533 1536 for for IN 1537 1544 further further JJ 1545 1555 activation activation NN 1556 1568 requirements requirement NNS 1569 1571 in in IN 1572 1575 the the DT 1576 1583 neonate neonate NN 1583 1584 . . .