Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Molecular and functional characterization of alloantigen-specific anergic T-cell suitable for cell therapy

ABSTRACT: IL-10 is an immunomodulant cytokine that plays a central role in controlling inflammation, down-regulating immune responses, and inducing immunological tolerance. IL-10 inhibits the expression of costimulatory molecules and the secretion of inflammatory cytokines by antigen-presenting cells (APC), directly suppresses T-cell proliferation, and promotes T-cell anergy. In this study we demonstrate that IL-10 inhibits primary allogeneic proliferation in total PBMC and induces antigen(Ag)-specific T-cell hyporesponsiveness. IL-10-induced anergy is TGF-beta independent, is associated with a decrease of Ag-specific CTLp frequency, and can be obtained among cells with different degree of HLA disparity. The use of tolerogenic dendritic cells (DC) differentiated in the presence of IL-10 (DC-10) allows a more consistent anergy induction, even in the context of HLA matched donors. Importantly, alloAg-IL-10/DC-10-anergized T cells preserve their ability to respond to nominal and third party Ags. Microarray experiments were conducted on different mixed lymphocyte cultures aiming at the identification of gene expression profiles characteristic for the various T cell populations. Independently from the APC used to anergized T cells, the resulting T cell populations exhibit a specific gene signature. Based on the results of this study, we developed a method suitable for GMP scale up and for the generation of a population of anergic Ag-specific T cells for cellular therapy. The dataset comprises 12 samples divided into four sample groups each representing a certain kind of allogeneic mixed lymphocyte culture, i.e. peripheral blood mononuclear cells (PBMC) mixed with CD3-depleted cells (MEC, monocyte-enriched cells) with or without IL-10 treatment, and PBMC mixed with mature or IL-10 treated dendritic cells (DCs). Each group includes three biological replicates with cells collected from different donors.

ORGANISM(S): Homo sapiens

SUBMITTER: Stefan Tomiuk

PROVIDER: E-GEOD-17493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Molecular and functional characterization of alloantigen-specific anergic T-cell suitable for cell therapy

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