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Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies.

Abstract：

BACKGROUND & AIMS:Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease usually requiring life-long immunosuppression. The mechanisms for disease initiation and chronicity are largely unknown. A contribution of deficient regulatory T cells (Tregs) in the blood was controversially discussed recently. So far investigations in the target organ have been limited to single parameter analysis in untreated AIH. METHODS:We retrospectively analysed the pattern of liver infiltrating T, B and regulatory T cells quantitatively with simultaneous multicolour immunofluorescence before (n=45) and under (n=31) therapy in adult AIH type 1 (AIH-1) patients. RESULTS:Intrahepatic CD4(+) cells dominate over CD8(+) at diagnosis, but with increasing disease activity the CD4(+)/CD8(+) ratio approached one. While there is no change of Tregs in the blood, they are enriched with effector T cells (Teffs) within the liver of patients with untreated AIH-1 with a constant Treg/Teff ratio. Even more importantly, immunosuppression mostly with steroids and azathioprine caused a disproportional loss of intrahepatic Tregs. Patients reaching biochemical remission had higher intrahepatic Treg/Teff and Treg/B cell ratios compared to patients failing to reach remission. In vitro proliferation of Tregs seemed to be more suppressed by prednisolone than expansion of Teffs. Furthermore, intraportal B cells correlated with serum IgG suggesting an autochthonous intrahepatic IgG production. CONCLUSIONS:Intrahepatic Tregs are rather enriched than numerically deficient in untreated AIH-1. The disproportional decrease of intrahepatic Tregs during therapy might explain high relapse rates after discontinuation of immunosuppression. Thus, future therapies increasing intrahepatic immunoregulation might be better suited for long-term control of AIH.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Taubert R,Hardtke-Wolenski M,Noyan F,Wilms A,Baumann AK,Schlue J,Olek S,Falk CS,Manns MP,Jaeckel E

doi

10.1016/j.jhep.2014.05.034

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

1106-14

issue

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(14)00381-X

journal_volume

pub_type

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Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies.