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 (PIF ) 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 PIF block PHA-induced PBMC proliferation and promote anti-inflammatory IL10 secretion, while reducing pro-inflammatory IFNγ secretion. Thus favoring a T 2 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 Ca 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 PIF offers improved target specificity as compared to PIF . Collectively, PIF directly regulates mitogen-induced PBMC activation. Results support PIF translation for therapy of immune disorders. 9&15 9&15 H 15 9 2+

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:	30 Mar 2021 21:15
URI:	http://repository.essex.ac.uk/id/eprint/12780

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