Phenotypic evaluation of CD28 negative T cells in primary sclerosing cholangitis
-
1
University of Birmingham, Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, United Kingdom
-
2
Medical Research Council Centre for Immune Regulation, School of Immunity & Infection, Institute of Biomedical Research,, United Kingdom
-
3
Friedrich Schiller University of Jena, Germany
Background/Aims: Genetic, functional and epidemiologic studies implicate CD28 and vitamin D (vitD) as relevant to autoimmune diseases including primary sclerosing cholangitis (PSC). Here we studied the role of CD28-ve T cells in PSC and the effects of vitD on their phenotype. Methods: Liver-infiltrating (LIMCs) and peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors or patients with PSC. The frequency and phenotype of CD28-ve cells [expression of activation (CD69, CD25) and exhaustion (PD-1) markers, perforin and granzyme B] were studied by flow cytometry. PSC LIMCs and PBMCs were activated and the release of IFNγ was examined. CD28-ve and CD28+ve cells from PSC PBMCs were stimulated with anti-CD3, autologous CD14+monocytes (5:1 ratio) with/without vitD for 4 days. Results: CD4+CD28-ve and CD8+CD28-ve T cells were highly expanded in PSC peripheral blood (3.9- and 2.1-fold increase respectively versus normal blood) and in PSC liver (17.8- and 2.45-fold increase respectively versus normal liver). The frequency of CD4+CD28-ve T cells in PSC liver was significantly higher than PSC peripheral blood (p<0.01). Liver-infiltrating CD4+CD28-ve T cells showed an activated CD25+CD69+PD-1- and cytotoxic phenotype granzymeB+perforin+. In-vitro stimulation of PSC liver-infiltrating CD4+CD28-ve cells induced the production of IFNγ (41%), which was much higher compared to their CD28+ve counterparts (12%). Stimulation of PSC peripheral blood CD28-ve and CD28+ve cells with vitD induced CD28 expression on CD28-ve (+52%) and CD28+ve (+65%) cells and suppressed IFNγ production (-43% and 67%, respectively). Conclusion: In PSC, CD28 negative T cells are pro-inflammatory, an effect that can be reduced by vitamin D supplementation.
References
Krones E., et al, Liver Int. 2012; 32(3):352-269
Ludwig J., et al, Hepatology 1981
Bo X., et al., Gut 2001; 49: 131-141
Weng NP., et al, Trends Immunol 2009; 30(7):306-312
Keywords:
Vitamin D,
CD28null,
primary sclerosing cholangitis,
biliary epithelial cells,
Cytotoxicity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Liaskou
E,
Jeffery
L,
Suresh
S,
Trivedi
P,
Bruns
T,
Adams
D and
Sansom
D
(2013). Phenotypic evaluation of CD28 negative T cells in primary sclerosing cholangitis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00085
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Evaggelia Liaskou, University of Birmingham, Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, Birmingham, United Kingdom, e.liaskou@bham.ac.uk