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Vol. 28, No. 1, 2010
Issue release date: May 2010
Section title: Immunology and Liver Disease
Dig Dis 2010;28:63–69
(DOI:10.1159/000282066)

Adaptive Immunity in Autoimmune Hepatitis

Longhi M.S. · Ma Y. · Mieli-Vergani G. · Vergani D.
aInstitute of Liver Studies and bPaediatric Liver Centre, King’s College London School of Medicine at King’s College Hospital, London, UK

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Article / Publication Details

First-Page Preview
Abstract of Immunology and Liver Disease

Published online: 5/7/2010

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI

Abstract

The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of αβ-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (TH0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, TH0 lymphocytes can differentiate into TH1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into TH2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25high regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses.


  

Author Contacts

Prof. Diego Vergani
Institute of Liver Studies, King’s College Hospital
Denmark Hill, London SE5 9RS (UK)
Tel. +44 203 299 3305, Fax +44 203 299 3700
E-Mail diego.vergani@kcl.ac.uk

  

Article Information

Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 0, Number of References : 47

  

Publication Details

Digestive Diseases (Clinical Reviews)

Vol. 28, No. 1, Year 2010 (Cover Date: May 2010)

Journal Editor: Malfertheiner P. (Magdeburg)
ISSN: 0257-2753 (Print), eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI


Article / Publication Details

First-Page Preview
Abstract of Immunology and Liver Disease

Published online: 5/7/2010

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 0

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI


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