!Name=Diehn et al,(2002): T-cell co-stimulation !ExptSetNo=748 !Description=Optimal activation of T cells requires effective occupancy of both the antigen-specific T cell receptor and a second coreceptor such as CD28. We used cDNA microarrays to characterize the genomic expression program in human peripheral T cells responding to stimulation of these receptors. We found that CD28 agonists alone elicited few, but reproducible, changes in gene expression, whereas CD3 agonists elicited a multifaceted temporally choreographed gene expression program. The principal effect of simultaneous engagement of CD28 was to increase the amplitude of the CD3 transcriptional response. The induced genes whose expression was most enhanced by costimulation were significantly enriched for known targets of nuclear factor of activated T cells (NFAT) transcription factors. This enhancement was nearly abolished by blocking the nuclear translocation of NFATc by using the calcineurin inhibitor FK506. CD28 signaling promoted phosphorylation, and thus inactivation, of the NFAT nuclear export kinase glycogen synthase kinase-3 (GSK3), coincident with enhanced dephosphorylation of NFATc proteins. These results provide a detailed picture of the transcriptional program of T cell activation and suggest that enhancement of transcriptional activation by NFAT, through inhibition of its nuclear export, plays a key role in mediating the CD28 costimulatory signal. !Name=Control, 00.00 hr. T-Cell !Exptid=15383 !Name=Control, 01.00 hr. T-Cell !Exptid=15384 !Name=Control, 02.00 hr. T-Cell !Exptid=15385 !Name=Control, 06.00 hr. T-Cell !Exptid=15386 !Name=Control, 12.00 hr. T-Cell !Exptid=15387 !Name=Control, 24.00 hr. T-Cell !Exptid=15388 !Name=Control, 48.00 hr. T-Cell !Exptid=15389 !Name=CD3 beads 00.00 hr. T-Cell !Exptid=15397 !Name=CD3 beads 01.00 hr. T-Cell, Repeat. !Exptid=16472 !Name=CD3 beads 02.00 hr. T-Cell !Exptid=15399 !Name=CD3 beads 06.00 hr. T-Cell !Exptid=15400 !Name=CD3 beads 12.00 hr. T-Cell !Exptid=15438 !Name=CD3 beads 24.00 hr. T-Cell !Exptid=15445 !Name=CD3 beads 48.00 hr. T-Cell !Exptid=15457 !Name=CD28 beads 00.00 hr. T-Cell !Exptid=15521 !Name=CD28 beads 01.00 hr. T-Cell !Exptid=15523 !Name=CD28 beads 02.00 hr. T-Cell !Exptid=15525 !Name=CD28 beads 06.00 hr. T-Cell !Exptid=15527 !Name=CD28 beads 12.00 hr. T-Cell !Exptid=15529 !Name=CD28 beads 24.00 hr. T-Cell !Exptid=15532 !Name=CD28 beads 48.00 hr. T-Cell !Exptid=15533 !Name=CD3 + CD28 beads 00.00 hr. T-Cell !Exptid=15463 !Name=CD3 + CD28 beads 01.00 hr. T-Cell; trunc. !Exptid=15465 !Name=CD3 + CD28 beads 02.00 hr. T-Cell !Exptid=15467 !Name=CD3 + CD28 beads 06.00 hr. T-Cell !Exptid=15468 !Name=CD3 + CD28 beads 12.00 hr. T-Cell !Exptid=15469 !Name=CD3 + CD28 beads 24.00 hr. T-Cell !Exptid=15481 !Name=CD3 + CD28 beads 48.00 hr. T-Cell !Exptid=15482 !Name=I + P T-Cell 00.00 hr. !Exptid=15390 !Name=I + P T-Cell 01.00 hr. !Exptid=15391 !Name=I + P T-Cell 02.00 hr. !Exptid=15392 !Name=I + P T-Cell 06.00 hr. !Exptid=15393 !Name=I + P T-Cell 12.00 hr. !Exptid=15394 !Name=I + P T-Cell 24.00 hr. !Exptid=15395 !Name=I + P T-Cell 48.00 hr. !Exptid=15396 !Name=PHA, 00.00 hr. T-Cell, Repeat. !Exptid=16190 !Name=PHA, 01.00 hr. T-Cell, Repeat. !Exptid=16195 !Name=PHA, 02.00 hr. T-Cell, Repeat. !Exptid=16200 !Name=PHA, 06.00 hr. T-Cell, Repeat. !Exptid=16204 !Name=PHA, 12.00 hr. T-Cell, Repeat. !Exptid=16207 !Name=PHA, 24.00 hr. T-cell !Exptid=15791 !Name=PHA, 48.00 hr. T-Cell, Repeat. !Exptid=16211 !Name=CD3 + CD28 beads + FK506 01.00 hr. T-cell !Exptid=15560 !Name=CD3 + CD28 beads + FK506 02.00 hr. T-cell !Exptid=15561 !Name=CD3 + CD28 beads + FK506 06.00 hr. T-cell !Exptid=15562 !Name=CD3 + CD28 beads + FK506 12.00 hr. T-cell !Exptid=15563 !Name=CD3 + CD28 beads + FK506 24.00 hr. T-cell !Exptid=15564 !Name=CD3 + CD28 beads + FK506 48.00 hr. T-cell !Exptid=15565 !Name=TNF-alpha, 02.00 hr. T-cell. !Exptid=15694 !Name=TNF-alpha, 12.00 hr. T-cell. !Exptid=15700 !Name=TNF-alpha, 24.00 hr. T-cell. !Exptid=15704 !Name=Interferon gamma, 02.00 hr. T-cell * !Exptid=15952 !Name=Interferon gamma, 12.00 hr. T-cell * !Exptid=15953 !Name=Interferon gamma, 24.00 hr. T-cell * !Exptid=15954 !Name=072801 Time Zero Z2 T-Cell !Exptid=18916 !Name=072801 Time Zero Z3 T-Cell !Exptid=18914 !Name=072801 Mock 01.00 hr. T-Cell !Exptid=18925 !Name=072801 Mock 02.00 hr. T-Cell !Exptid=18938 !Name=072801 Mock 06.00 hr. T-Cell !Exptid=18935 !Name=072801 Mock 12.00 hr. T-Cell !Exptid=18896 !Name=072801 B7-2 01.00 hr. T-Cell !Exptid=18899 !Name=072801 B7-2 02.00 hr. T-Cell !Exptid=18930 !Name=072801 B7-2 06.00 hr. T-Cell !Exptid=18958 !Name=072801 B7-2 12.00 hr. T-Cell !Exptid=18921 !Name=072801 100% CD28 beads 01.00 hr. T-Cell !Exptid=18926 !Name=072801 100% CD28 beads 02.00 hr. T-Cell !Exptid=18932 !Name=072801 100% CD28 beads 06.00 hr. T-Cell !Exptid=18902 !Name=072801 100% CD28 beads 12.00 hr. T-Cell !Exptid=18934