Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human Treg cell versus their controls in human and mouse

ABSTRACT: We applied Affymetrix GeneChip technology for expression profiling of CD4+CD25+ (Treg) T cells versus their naive CD4+CD25- controls to obtain more information about the underlying molecular mechanisms involved in Treg specific immune suppression Experiment Overall Design: Expression profiles from: Experiment Overall Design: [1] human Treg cells obtained from peripheral blood by cell sorting were compared to their naive controls. RNAs were prepared from pools of ten individual healthy donors, labeled in two independend labeling reactions and hybridized onto two GeneChips of the same lot. Experiment Overall Design: [2] mouse Treg cells obtained from spleen by cell sorting of Balb/c mice were compared to their naive controls. RNAs were prepared from pools of three individual Balb/c mice, labeled in three independend labeling reactions and hybridized onto three GeneChips of the same lot. Experiment Overall Design: The differences in gene expression were used to unravel molecular mechanisms that help to explain the suppressive and anergic phenotypes of Treg cells after antigen activation.

ORGANISM(S): Mus musculus

SUBMITTER: Robert Geffers

PROVIDER: E-GEOD-4571 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Signatures of human regulatory T cells: an encounter with old friends and new players.

Pfoertner Susanne S Jeron Andreas A Probst-Kepper Michael M Guzman Carlos A CA Hansen Wiebke W Westendorf Astrid M AM Toepfer Tanja T Schrader Andres J AJ Franzke Anke A Buer Jan J Geffers Robert R

Genome biology 20060101 7

<h4>Background</h4>Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined.<h4>Results</h4>To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (H ...[more]

PMID: 16836768

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Project description:Regulatory T (Treg) cells play an important role in the induction and maintenance of peripheral tolerance. Treg cells also suppress a variety of other immune responses, including anti-tumor and alloimmune responses. We have previously reported that tumor-activated Treg cells express granzyme B and that granzyme B is important for Treg cell-mediated suppression of anti-tumor immune responses (GSE13409). Here, we report that allogeneic mismatch also induces the expression of granzyme B. Granzyme B-deficient mice challenged with fully mismatched allogeneic P815 mastocytoma cells have markedly improved survival compared to WT and other granzyme- or perforin-deficient mice, suggesting an immunoregulatory role for granzyme B in this setting. Treg cells harvested from the tumor environment of P815-challenged mice express granzyme B. Treg cells also express granzyme B in vitro during mixed lymphocyte reactions and in vivo in a mouse model of graft-versus-host disease (GVHD). However, in contrast to findings from our previously published tumor model, granzyme B is not required for the suppression of effector T cell (Teff) proliferation in in vitro Treg suppression assays stimulated by either Concanavalin A or allogeneic antigen presenting cells. Additionally, in an ex vivo assay, sort-purified in vivo-activated CD4+Foxp3+ Treg cells from mice with active GVHD -- under conditions known to induce granzyme B expression in Treg cells -- suppressed Teff cell proliferation in a granzyme B-independent manner. Adoptive transfer of naive granzyme B-deficient CD4+CD25+ Treg cells into a mouse model of GVHD rescued hosts from lethatlity equivalently to naive wild-type Treg cells. Serum analysis of GVHD-associated cytokine production in these recipients also demonstrated that Treg cells suppressed production of IL-2, IL-4, IL-5, GM-CSF, and IFN-gamma in a granzyme B-independent manner. In order to determine whether the context in which Treg cells are activated alters the intrinsic properties of Treg cells, we used Foxp3 reporter mice to obtain gene expression profiles of CD4+Foxp3+ Treg cells purifed from naive resting spleens, spleens from mice with acute GVHD, and from ascites fluid of mice challenged intraperitoneally with allogeneic P815 tumor cells. Unsupervised analyses revealed distinct activation signatures of Treg cells among the 3 experimental groups. Taken together, these findings demonstrate that granzyme B is not required for Treg cell-mediated suppression of GVHD, which is in contrast to what we have previously reported for Treg cell function in the setting of tumor challenge. Cell intrinsic differences could partially account for these differential phenotypes. These data also suggest the therapeutic potential of targeting specific Treg cell suppressive functions in order to segregate GVHD and graft-versus-tumor effector functions. Experiment Overall Design: Six replicates of Naive CD4+Foxp3+ Treg cells were purified from resting spleens, five replicates of allogeneic tumor-activated Treg cells and three samples of GVHD-activated Treg cells. Experiment Overall Design: Naive reps 1-3 are controls for the GVHD-activated samples. Experiment Overall Design: Naive reps 4-6 are controls for the Allogeneic tumor-activated samples.

Dataset Information

Transcription profiling of human Treg cell versus their controls in human and mouse

Publications

Signatures of human regulatory T cells: an encounter with old friends and new players.

Similar Datasets

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