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Expression data from healthy control human peripheral blood mononuclear cells (PBMC) treated with wild-type IL-2 or F42K

ABSTRACT: IL-2 mutant (F42K) is a variant of IL-2 that binds preferentially to the lower affinity IL-2Rβγ and has minimal binding to CD25, on Tregs, effector NK and T-cell subsets. Our recent study has uncovered that in contrast to WT IL-2, F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs in PBMC from healthy controls and melanoma patients whereas it did promote the expansion of NK cells. We used microarray to study the differences of gene profiles induced by wild-type (WT) IL-2, F42K and IL-15 when treated on freshly isolated human peripheral blood mononuclear cells (PBMC) from healthy control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77601 | GEO | 2016/09/01

SECONDARY ACCESSION(S): PRJNA310996

REPOSITORIES: GEO

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Expression data from healthy control human peripheral blood mononuclear cells (PBMC) treated with wild-type IL-2 or F42K

Project description:IL-2 mutant (F42K) is a variant of IL-2 that binds preferentially to the lower affinity IL-2RÎ²Î³ and has minimal binding to CD25, on Tregs, effector NK and T-cell subsets. Our recent study has uncovered that in contrast to WT IL-2, F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs in PBMC from healthy controls and melanoma patients whereas it did promote the expansion of NK cells. We used microarray to study the differences of gene profiles induced by wild-type (WT) IL-2, F42K and IL-15 when treated on freshly isolated human peripheral blood mononuclear cells (PBMC) from healthy control. Human peripheral blood mononuclear cells (PBMC) were isolated from buffy coat and were stimulated with 0.4nM WT IL-2, F42K or IL-15 for 24 hr. Total RNA was extracted from each WT IL-2, F42K and IL-15 treated PBMCs and Sense RNA was reverse-transcribed via RT reaction into DNA and labeled with biotin using Affymetrix labeling kits and hybridized on human Affymetrix microarray chip.

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Transcription profiling of human PBMC treated with anti-CD25 mAb

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Project description:Low-dose IL-2 represents an immunotherapy to selectively expand regulatory T cells (Tregs) to promote tolerance in patients with autoimmunity. In this article, we show that a fusion protein (FP) of mouse IL-2 and mouse IL-2Rα (CD25), joined by a noncleavable linker, has greater in vivo efficacy than rIL-2 at Treg expansion and control of autoimmunity. Biochemical and functional studies support a model in which IL-2 interacts with CD25 in the context of this FP in trans to form inactive head-to-tail dimers that slowly dissociate into an active monomer. In vitro, IL-2/CD25 has low sp. act. However, in vivo IL-2/CD25 is long lived to persistently and selectively stimulate Tregs. In female NOD mice, IL-2/CD25 administration increased Tregs within the pancreas and reduced the instance of spontaneous diabetes. Thus, IL-2/CD25 represents a distinct class of IL-2 FPs with the potential for clinical development for use in autoimmunity or other disorders of an overactive immune response.

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Project description:NK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent. To identify Runx3 responsive genes, NK cells were isolated from spleen of WT and Runx3-/- mice . Ten samples (5 WT and 5 Runx3-/-) of freshly isolated NK cells were separately obtained from individual mice. Cells were cultured for 7 days with IL-2 or IL-15.

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