Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of cultured Vd1 and Vd2 gd T cells following non-TCR agonist stimulation

ABSTRACT: The two major human gd T cell subsets, Vd1 and Vd2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vd1 and Vd2 cells from the same PBL preparation to levels sufficient for sorting and microarray analysis. Although the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614 genes were identified, which were differentially expressed in the two subsets, from two donors, respectively. Approximately 4,500 genes changed in both subsets following PMA/ionomycin treatment; about 50% of these genes were subset-specific. Both subsets responded to a crude LPS preparation, but only 6% of the responsive genes were the same. The differentially expressed genes were consistent with Vd2 cells being more inflammatory and Vd1 cells having more of a regulatory phenotype. Both subsets expressed transcripts encoding an array of innate and NK cell receptors, supporting the relationship of gd?T cells to the innate immune system. Our results show that circulating Vd1 and Vd2 subsets in humans have considerable, inherent differences in gene expression following treatment with non-TCR agonists, supporting unique functional roles for these cells in vivo.

ORGANISM(S): Homo sapiens

SUBMITTER: Ellen Kress

PROVIDER: E-GEOD-3720 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Distinct gene expression in human Vdelta1 and Vdelta2 gammadelta T cells following non-TCR agonist stimulation.

Kress Ellen E Hedges Jodi F JF Jutila Mark A MA

Molecular immunology 20060119 12

The two major human gammadelta T cell subsets, Vdelta1 and Vdelta2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vdelta1 and Vdelta2 cells from the same PBL preparation to levels sufficien ...[more]

PMID: 16423401

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Project description:gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.

Dataset Information

Transcription profiling of cultured Vd1 and Vd2 gd T cells following non-TCR agonist stimulation

Publications

Distinct gene expression in human Vdelta1 and Vdelta2 gammadelta T cells following non-TCR agonist stimulation.

Similar Datasets

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