Barnea, ER and Kirk, D and Todorova, K and McElhinney, J and Hayrabedyan, S and Fernández, N (2015) 'PIF direct immune regulation: Blocks mitogen-activated PBMCs proliferation, promotes T<inf>H</inf>2/T<inf>H</inf>1 bias, independent of Ca²⁺.' Immunobiology, 220 (7). 865 - 875. ISSN 0171-2985

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Abstract

PreImplantation Factor (PIF9&15) secreted by viable embryos exerts an essential transplant acceptance and immune regulatory role in pregnancy. Synthetic PIF replicates endogenous PIF's effect in pregnant and non-pregnant immune disorder models. PIF binds macrophages to regulate CD3/CD28-induced T-cell response. We present evidence that PIF regulates the co-stimulatory T-cell receptor, CD2, which binds to and is activated by phytohemagglutinin (PHA), a potent mitogen, confirming PIF's ability to systemically respond to diverse immune stimulants. PIF's effect on PHA-activated PBMC (male and non-pregnant females) proliferation and cytokine secretion was tested, showing that both PIF9&15 block PHA-induced PBMC proliferation and promote anti-inflammatory IL10 secretion, while reducing pro-inflammatory IFNγ secretion. Thus favoring a TH2 cytokine bias. Surface plasmon resonance spectroscopy, immunocytochemistry and Flex station experiments reveal that PIF effect is direct. PIF targets intracellular targets but does not affect early Ca2+ mobilization. By promoting the CD2 receptor in activated T-cells and through inhibition of co-ligand CD58 expression, PIF regulates antigen-presenting cell (APC)-T-cell interactions required for PHA action. Structure-based design demonstrated that PIF15 offers improved target specificity as compared to PIF9. Collectively, PIF directly regulates mitogen-induced PBMC activation. Results support PIF translation for therapy of immune disorders.

Item Type:	Article
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science and Health > Life Sciences, School of
Depositing User:	Jim Jamieson
Date Deposited:	10 Feb 2015 12:46
Last Modified:	22 Jun 2021 21:15
URI:	http://repository.essex.ac.uk/id/eprint/12780

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