Z Gastroenterol 2020; 58(01): e59-e60
DOI: 10.1055/s-0039-3402266
Poster Visit Session V Viral Hepatitis and Immunology: Saturday, February 15, 2020, 11:00 am – 11:45 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Cirrhosis and acute-on-chronic liver failure are linked with aberrant expression of co-stimulatory markers on T-cells

S Rueschenbaum
1   University Hospital Essen, Department for Gastroenterology and Hepatology, Essen, Germany
,
A Queck
2   Goethe-University Hospital Frankfurt, Department of Internal Medicine 1, Frankfurt am Main, Germany
,
K Schwarzkopf
2   Goethe-University Hospital Frankfurt, Department of Internal Medicine 1, Frankfurt am Main, Germany
,
B Brüne
3   Goethe-University Frankfurt, Institute of Biochemistry 1, Frankfurt, Germany
,
C Welsch
2   Goethe-University Hospital Frankfurt, Department of Internal Medicine 1, Frankfurt am Main, Germany
,
H Wedemeyer
1   University Hospital Essen, Department for Gastroenterology and Hepatology, Essen, Germany
,
S Zeuzem
2   Goethe-University Hospital Frankfurt, Department of Internal Medicine 1, Frankfurt am Main, Germany
,
A Weigert
3   Goethe-University Frankfurt, Institute of Biochemistry 1, Frankfurt, Germany
,
C Lange
1   University Hospital Essen, Department for Gastroenterology and Hepatology, Essen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Introduction/Question:

A hallmark of liver cirrhosis is the occurrence of systemic inflammation and immunosuppression in parallel. These two opposite conditions are strongly enhanced during development of acute-on-chronic liver failure (ACLF). This is demonstrated by phenotypic changes of innate immune cells as well as their elevated cytokine production. However, little is known about phenotypic changes in the adaptive immune compartment. Therefore, we aimed to characterize T cells of patients with liver cirrhosis and ACLF with regards to co-stimulatory and inhibitory marker expression and cytokine production.

Methods:

Peripheral blood mononuclear cells (PBMCs) were isolated from liver cirrhosis and ACLF patients and healthy donor buffy coats. For marker analysis, cells were stained for a total of 23 co-stimulatory and inhibitory cell surface markers. For cytokine response, PBMCs were stimulated with PMA/Ionomycin and stained intracellular for IFNgamma and TNFalpha. All samples were analyzed by flow cytometry.

Results:

Flow cytometric analysis of CD8+, CD4+ and regulatory (CD4+ CD25dim CD127-) T cells revealed changes in marker expression specific for the subtypes. Liver cirrhosis and ACLF patients showed lower frequencies of CD27+ CD8+ T cells, but higher frequencies of CD8+ T cells containing the inhibitory marker KLRG1. Frequencies of OX-40+ CD4+ T cells were elevated in patients but also higher frequencies of CD4+ T cells carrying the inhibitory marker 2B4 were observed. Regulatory T cells of patients were characterized as containing higher frequencies of CD28+, GITR+ and CTLA-4+ cells. All mentioned cell types displayed higher frequencies of the death receptor CD95 and the inhibitory receptor PDPN suggesting an overall situation of immunosuppression. In agreement, CD8+ and CD4+ T cells showed decreased or even lost capabilities of elevated IFNgamma and TNFalpha production after stimulation in vitro.

Conclusions:

Our results display dysfunctional T cell cytokine responses in liver cirrhosis and ACLF as a possible background for patients' susceptibility to infections. As a potential mechanism, we could identify an aberrant expression of co-stimulatory and inhibitory markers on all T cell subsets suggesting a shift towards immunosuppression and higher cell death rates. Combined immunophenotyping of all PBMCs could identify the distinct pathways responsible for immunosuppression in patients as potential targets for precise immunotherapy.