Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse allogeneic cells after treatment with organ-derived dendritic cells

ABSTRACT: Transcriptional response of murine allogeneic T cells (B10.BR) after; stimulation with different organ-derived (spleen, liver, peripheral and; mesenteric lymph nodes) dendritic cells (C57BL/6) in vitro Experiment Overall Design: We stimulated B10.BR T cells with dendritic cells derived from different C57BL/6 organs for four days and then performed array experiments on the T cells.

ORGANISM(S): Mus musculus

SUBMITTER: Jeremy Grubin

PROVIDER: E-GEOD-5503 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Organ-derived dendritic cells have differential effects on alloreactive T cells.

Kim Theo D TD Terwey Theis H TH Zakrzewski Johannes L JL Suh David D Kochman Adam A AA Chen Megan E ME King Chris G CG Borsotti Chiara C Grubin Jeremy J Smith Odette M OM Heller Glenn G Liu Chen C Murphy George F GF Alpdogan Onder O van den Brink Marcel R M MR

Blood 20080104 5

Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target o ...[more]

PMID: 18178870

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Project description:Introduction: Expansion of antigen (Ag)-specific natural occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloAg-specific nTregs. Methods: A highly enriched nTreg-fraction (CD4+CD25brightCD127- T cells) was alloAg-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDC) or peripheral blood mononuclear cells (PBMC). The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the TSDR of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4 and cytokines. In addition, the antigen-specific suppressive capacity of these expanded nTregs was tested. Results: Allogeneic mature moDC and skin-derived DC were superior in inducing nTreg-expansion compared to immature moDC or PBMC in an HLA-DR and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2, could facilitate optimal mature moDC-induced nTreg-expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloAg-induced proliferation without significant suppression of completely HLA-mismatched-Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the TSDR within the FOXP3 gene and highly expressed of FOXP3, HELIOS and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-g and TNF-a but very few IL-17 producing nTregs were found. Next generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Conclusions: Human allogeneic mature moDC are highly efficient stimulator cells, in presence of exogenous IL-15, for expansion of stable alloAg-specific nTregs with superior suppressive function. Four different batches of highly pure regulatory T cells (all from the same donor) were expanded in two different ways, and compared to non-expanded samples.

Dataset Information

Transcription profiling of mouse allogeneic cells after treatment with organ-derived dendritic cells

Publications

Organ-derived dendritic cells have differential effects on alloreactive T cells.

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