Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612853
Poster Visit Session V Viral Hepatitis and Immunology – Saturday, January 27, 2018, 11:00am – 11:45am, Foyer area East Wing
Georg Thieme Verlag KG Stuttgart · New York

Analysis of unconventional T cells identifies intrahepatic type II NKT cells adapting a pro-inflammatory role in autoimmune hepatitis

M Sebode
1   University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Hamburg
,
C Schramm
1   University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Hamburg
,
L Fischer
2   University Medical Center Hamburg-Eppendorf, Department of Hepatobiliary Surgery and Transplantation, Hamburg
,
A Lohse
1   University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Hamburg
,
P Arrenberg
1   University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Hamburg
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Question:

The role of unconventional T cells like natural killer T (NKT) cells, gamma-delta (gd) T cells und mucosal associated invariant T (MAIT) was analyzed in human autoimmune liver diseases (AILD). So far, NKT cells have been mainly characterized in mouse models and are subdivided into pathogenic type I NKT cells and more protective type II NKT cells with immunoregulatory potential.

Methods:

The frequency and cytokine profile of peripheral and intrahepatic unconventional T cells from patients with the AILD autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were analyzed by flow cytometry. Healthy liver tissue of the resection margin of liver adenomas and liver biopsies from patients with drug-induced liver injury (DILI) served as control groups. Type I and type II NKT cells were specifically stained by a-galactosylceramide- and sulfatide-loaded human CD1 d-tetramers, respectively. MAIT cells were defined by antibody staining of CD161 and Va7.2, an a-chain segment of their semi-invariant T cell receptor. An antibody against the gamma- and delta chains of the TCR was used to stain gd T cells.

Results:

For peripheral gd T and MAIT cells a lower frequency for patients with AILD and DILI compared to healthy controls was detected. Within the liver, the frequency of gd T and MAIT cells did not differ significantly between patients with AILD and control groups. AIH patients revealed an increased frequency of peripheral type II NKT in comparison to control groups (0.11% of peripheral leukocytes vs. 0.05%, p = 0.02). An increased number of intrahepatic type II NKT in patients with AIH (3.78% of intrahepatic leukocytes) in comparison to healthy controls (1.82%) and patients with DILI (2.07%, p = 0.02) was also detected. Intrahepatic, but not peripheral type II NKT of AIH patients had a different cytokine profile than healthy controls with an increase of TNFa (77.8% vs. 59.1%, p = 0.03) and a decrease of IFNg (32.7% vs. 63.0%, p = 0.02). The cytokine profile of intrahepatic classical, conventional T cells did not differ significantly between AIH patients and control groups.

Conclusions:

This is the first analysis of type II NKT cells, reactive to the self-antigen sulfatide, in human AILD. In contrast to mouse models that have characterized type II NKT cells as being more protective, type II NKT cells exhibit a pronounced production of TNFa in livers of human AIH and could thus contribute to the pro-inflammatory mechanisms of AIH.