0	16	IL-2-independent	il-2-independent	JJ
17	27	activation	activation	NN
28	31	and	and	CC
32	45	proliferation	proliferation	NN
46	48	in	in	IN
49	54	human	human	JJ
55	56	T	t	NN
57	62	cells	cell	NNS
63	70	induced	induce	VBN
71	73	by	by	IN
74	78	CD28	cd28	NN
78	79	.	.	.

81	89	Although	although	IN
90	93	the	the	DT
94	98	role	role	NN
99	101	of	of	IN
102	106	CD28	cd28	NN
107	109	in	in	IN
110	111	T	t	NN
112	116	cell	cell	NN
117	130	costimulation	costimulation	NN
131	133	is	be	VBZ
134	140	firmly	firmly	RB
141	152	established	establish	VBN
152	153	,	,	,
154	157	the	the	DT
158	168	mechanisms	mechanism	NNS
169	171	by	by	IN
172	177	which	which	WDT
178	180	it	it	PRP
181	187	exerts	exert	VBZ
188	191	its	its	PRP$
192	205	costimulatory	costimulatory	JJ
206	213	actions	action	NNS
214	217	are	be	VBP
218	222	less	less	RBR
223	228	clear	clear	JJ
228	229	.	.	.

230	232	In	in	IN
233	237	many	many	JJ
238	251	circumstances	circumstance	NNS
252	254	it	it	PRP
255	257	is	be	VBZ
258	267	difficult	difficult	JJ
268	270	to	to	TO
271	282	distinguish	distinguish	VB
283	286	the	the	DT
287	294	effects	effect	NNS
295	297	of	of	IN
298	302	CD28	cd28	NN
303	307	from	from	IN
308	318	subsequent	subsequent	JJ
319	326	actions	action	NNS
327	329	of	of	IN
330	339	cytokines	cytokine	NNS
339	340	,	,	,
341	345	such	such	JJ
346	348	as	as	IN
349	353	IL-2	il-2	NN
353	354	,	,	,
355	357	on	on	IN
358	359	T	t	NN
360	364	cell	cell	NN
365	378	proliferation	proliferation	NN
378	379	.	.	.

380	384	Here	here	RB
384	385	,	,	,
386	388	we	we	PRP
389	395	report	report	VBP
396	397	a	a	DT
398	403	model	model	NN
404	406	of	of	IN
407	411	CD28	cd28	NN
412	425	costimulation	costimulation	NN
426	431	using	use	VBG
432	435	PMA	PMA	NNP
436	440	plus	plus	CC
441	444	the	the	DT
445	452	natural	natural	JJ
453	459	ligand	ligand	NN
460	464	CD80	cd80	NN
465	469	that	that	WDT
470	478	resulted	result	VBD
479	481	in	in	IN
482	486	very	very	RB
487	494	limited	limited	JJ
495	506	stimulation	stimulation	NN
507	509	of	of	IN
510	514	IL-2	il-2	NN
514	515	,	,	,
516	518	as	as	IN
519	528	evidenced	evidence	VBN
529	531	by	by	IN
532	536	both	both	CC
537	545	cytokine	cytokine	NN
546	556	production	production	NN
557	560	and	and	CC
561	565	IL-2	il-2	NN
566	574	promoter	promoter	NN
575	586	stimulation	stimulation	NN
586	587	.	.	.

588	596	Promoter	promoter	NN
597	603	assays	assay	NNS
604	612	revealed	reveal	VBD
613	627	CD28-dependent	cd28-dependent	JJ
628	635	effects	effect	NNS
636	638	on	on	IN
639	643	both	both	CC
644	653	NF-kappaB	NF-kappaB	NNP
654	657	and	and	CC
658	662	AP-1	ap-1	NN
662	663	,	,	,
664	667	but	but	CC
668	671	not	not	RB
672	674	on	on	IN
675	680	NF-AT	NF-AT	NNP
681	683	or	or	CC
684	687	the	the	DT
688	694	intact	intact	JJ
695	699	IL-2	il-2	NN
700	708	promoter	promoter	NN
708	709	.	.	.

710	712	In	in	IN
713	721	addition	addition	NN
721	722	,	,	,
723	724	T	t	NN
725	729	cell	cell	NN
730	743	proliferation	proliferation	NN
744	747	was	be	VBD
748	758	completely	completely	RB
759	768	resistant	resistant	JJ
769	771	to	to	TO
772	775	the	the	DT
776	783	actions	action	NNS
784	786	of	of	IN
787	790	the	the	DT
791	808	immunosuppressant	immunosuppressant	JJ
809	820	cyclosporin	cyclosporin	NN
821	822	A	A	NNP
823	824	(	(	(
824	827	CsA	CsA	NNP
827	828	)	)	)
828	829	.	.	.

830	838	Moreover	moreover	RB
839	840	T	t	NN
841	845	cell	cell	NN
846	859	proliferation	proliferation	NN
860	863	was	be	VBD
864	874	unaffected	unaffected	JJ
875	877	by	by	IN
878	881	the	the	DT
882	890	addition	addition	NN
891	893	of	of	IN
894	902	blocking	block	VBG
903	906	Abs	ab	NNS
907	909	to	to	TO
910	914	both	both	CC
915	919	IL-2	il-2	NN
920	923	and	and	CC
924	927	the	the	DT
928	932	IL-2	il-2	NN
933	941	receptor	receptor	NN
941	942	,	,	,
943	956	demonstrating	demonstrate	VBG
957	961	that	that	IN
962	966	this	this	DT
967	971	form	form	NN
972	974	of	of	IN
975	988	costimulation	costimulation	NN
989	991	by	by	IN
992	996	CD28	cd28	NN
997	1000	was	be	VBD
1001	1012	independent	independent	JJ
1013	1015	of	of	IN
1016	1020	IL-2	il-2	NN
1020	1021	.	.	.

1022	1024	We	we	PRP
1025	1029	also	also	RB
1030	1042	investigated	investigate	VBD
1043	1046	the	the	DT
1047	1054	effects	effect	NNS
1055	1057	of	of	IN
1058	1069	stimulating	stimulate	VBG
1070	1071	T	t	NN
1072	1076	cell	cell	NN
1077	1083	blasts	blast	NNS
1084	1088	with	with	IN
1089	1093	CD80	cd80	NN
1094	1099	alone	alone	RB
1100	1103	and	and	CC
1104	1109	found	find	VBD
1110	1114	that	that	IN
1115	1120	there	there	EX
1121	1124	was	be	VBD
1125	1126	a	a	DT
1127	1134	limited	limit	VBN
1135	1146	requirement	requirement	NN
1147	1150	for	for	IN
1151	1155	IL-2	il-2	NN
1156	1158	in	in	IN
1159	1163	this	this	DT
1164	1170	system	system	NN
1170	1171	.	.	.

1172	1174	We	we	PRP
1175	1183	conclude	conclude	VBP
1184	1188	that	that	IN
1189	1193	CD28	cd28	NN
1194	1207	costimulation	costimulation	NN
1208	1211	can	can	MD
1212	1217	cause	cause	VB
1218	1229	substantial	substantial	JJ
1230	1231	T	t	NN
1232	1236	cell	cell	NN
1237	1250	proliferation	proliferation	NN
1251	1253	in	in	IN
1254	1257	the	the	DT
1258	1265	absence	absence	NN
1266	1268	of	of	IN
1269	1273	IL-2	il-2	NN
1273	1274	,	,	,
1275	1280	which	which	WDT
1281	1283	is	be	VBZ
1284	1290	driven	drive	VBN
1291	1293	by	by	IN
1294	1295	a	a	DT
1296	1303	soluble	soluble	JJ
1304	1310	factor	factor	NN
1311	1322	independent	independent	JJ
1323	1325	of	of	IN
1326	1331	NF-AT	NF-AT	NNP
1332	1347	transactivation	transactivation	NN
1347	1348	.	.	.