Unknown,Transcriptomics,Genomics,Proteomics

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T-cell co-stimulation

ABSTRACT: 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. Groups of assays that are related as part of a time series. Using regression correlation

ORGANISM(S): Homo sapiens

SUBMITTER: Max Diehn

PROVIDER: E-GEOD-3630 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.

Diehn Maximilian M Alizadeh Ash A AA Rando Oliver J OJ Liu Chih Long CL Stankunas Kryn K Botstein David D Crabtree Gerald R GR Brown Patrick O PO

Proceedings of the National Academy of Sciences of the United States of America 20020823 18

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 ...[more]

PMID: 12195013

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T-cell co-stimulation

Publications

Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.

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