0	15	CTLA-4-Mediated	ctla-4-mediated	JJ
16	26	inhibition	inhibition	NN
27	29	of	of	IN
30	35	early	early	JJ
36	42	events	event	NNS
43	45	of	of	IN
46	47	T	t	NN
48	52	cell	cell	NN
53	66	proliferation	proliferation	NN
66	67	.	.	.

69	75	CTLA-4	ctla-4	NN
76	86	engagement	engagement	NN
87	89	by	by	IN
90	94	mAbs	mab	NNS
95	103	inhibits	inhibit	VBZ
103	104	,	,	,
105	110	while	while	IN
111	115	CD28	cd28	NN
116	124	enhances	enhance	NNS
124	125	,	,	,
126	130	IL-2	il-2	NN
131	141	production	production	NN
142	145	and	and	CC
146	159	proliferation	proliferation	NN
160	164	upon	upon	IN
165	166	T	t	NN
167	171	cell	cell	NN
172	182	activation	activation	NN
182	183	.	.	.

184	188	Here	here	RB
188	189	,	,	,
190	192	we	we	PRP
193	197	have	have	VBP
198	206	analyzed	analyze	VBN
207	210	the	the	DT
211	221	mechanisms	mechanism	NNS
222	230	involved	involve	VBN
231	233	in	in	IN
234	249	CTLA-4-mediated	ctla-4-mediated	JJ
250	260	inhibition	inhibition	NN
261	263	of	of	IN
264	265	T	t	NN
266	270	cell	cell	NN
271	281	activation	activation	NN
282	284	of	of	IN
285	290	naive	naive	JJ
291	295	CD4+	cd4+	JJ
296	297	T	t	NN
298	303	cells	cell	NNS
304	309	using	use	VBG
310	312	Ab	Ab	NNP
313	326	cross-linking	cross-linking	NN
326	327	.	.	.

328	334	CTLA-4	ctla-4	NN
335	343	ligation	ligation	NN
344	353	inhibited	inhibit	VBD
354	370	CD3/CD28-induced	cd3/cd28-induced	JJ
371	375	IL-2	il-2	NN
376	380	mRNA	mrna	NN
381	393	accumulation	accumulation	NN
394	396	by	by	IN
397	407	inhibiting	inhibit	VBG
408	412	IL-2	il-2	NN
413	426	transcription	transcription	NN
426	427	,	,	,
428	433	which	which	WDT
434	441	appears	appear	VBZ
442	444	to	to	TO
445	447	be	be	VB
448	456	mediated	mediate	VBN
457	459	in	in	IN
460	464	part	part	NN
465	472	through	through	IN
473	483	decreasing	decrease	VBG
484	489	NF-AT	nf-at	NN
490	502	accumulation	accumulation	NN
503	505	in	in	IN
506	509	the	the	DT
510	516	nuclei	nucleus	NNS
516	517	.	.	.

518	525	However	however	RB
525	526	,	,	,
527	533	CTLA-4	ctla-4	NN
534	542	ligation	ligation	NN
543	546	did	do	VBD
547	550	not	not	RB
551	557	appear	appear	VB
558	560	to	to	TO
561	567	affect	affect	VB
568	571	the	the	DT
572	585	CD28-mediated	cd28-mediated	JJ
586	599	stabilization	stabilization	NN
600	602	of	of	IN
603	607	IL-2	IL-2	NNP
608	612	mRNA	mRNA	NNP
612	613	.	.	.

614	621	Further	further	RB
621	622	,	,	,
623	629	CTLA-4	ctla-4	NN
630	640	engagement	engagement	NN
641	650	inhibited	inhibit	VBD
651	662	progression	progression	NN
663	670	through	through	IN
671	674	the	the	DT
675	679	cell	cell	NN
680	685	cycle	cycle	NN
686	688	by	by	IN
689	699	inhibiting	inhibit	VBG
700	703	the	the	DT
704	714	production	production	NN
715	717	of	of	IN
718	724	cyclin	cyclin	NN
725	727	D3	d3	NN
727	728	,	,	,
729	745	cyclin-dependent	cyclin-dependent	JJ
746	752	kinase	kinase	NNP
753	754	(	(	(
754	759	cdk)4	cdk)4	NN
759	760	,	,	,
761	764	and	and	CC
765	769	cdk6	cdk6	NN
770	774	when	when	WRB
775	778	the	the	DT
779	780	T	t	NN
781	786	cells	cell	NNS
787	791	were	be	VBD
792	802	stimulated	stimulate	VBN
803	807	with	with	IN
808	821	anti-CD3/CD28	anti-cd3/cd28	NN
822	825	and	and	CC
826	830	with	with	IN
831	839	anti-CD3	anti-cd3	NN
840	845	alone	alone	RB
845	846	.	.	.

847	852	These	these	DT
853	860	results	result	NNS
861	869	indicate	indicate	VBP
870	874	that	that	IN
875	881	CTLA-4	ctla-4	NN
882	891	signaling	signaling	NN
892	900	inhibits	inhibit	VBZ
901	907	events	event	NNS
908	913	early	early	RB
914	916	in	in	IN
917	918	T	t	NN
919	923	cell	cell	NN
924	934	activation	activation	NN
935	939	both	both	CC
940	942	at	at	IN
943	947	IL-2	il-2	NN
948	961	transcription	transcription	NN
962	965	and	and	CC
966	968	at	at	IN
969	972	the	the	DT
973	978	level	level	NN
979	981	of	of	IN
982	998	IL-2-independent	il-2-independent	JJ
999	1005	events	event	NNS
1006	1008	of	of	IN
1009	1012	the	the	DT
1013	1017	cell	cell	NN
1018	1023	cycle	cycle	NN
1023	1024	,	,	,
1025	1028	and	and	CC
1029	1033	does	do	VBZ
1034	1037	not	not	RB
1038	1044	simply	simply	RB
1045	1051	oppose	oppose	VB
1052	1065	CD28-mediated	cd28-mediated	JJ
1066	1079	costimulation	costimulation	NN
1079	1080	.	.	.