Assessment of intrahepatic regulatory T cells in children with autoimmune hepatitis

Ann Hepatol. 2016 Sep-Oct;15(5):682-90. doi: 10.5604/16652681.1212319.

Abstract

Background. T-cell populations regulate the balance of immune responses. The CD (Cluster of differentiation) 4+CD25+ regulatory T cells (Tregs) are crucial for maintaining negative control of various immune responses. There are different T-cell subpopulations with regulatory functions, as natural killer T cells, CD8+ and CD28. The forkhead box P3 (FOXP3) regulates Treg development and is required for its suppressive function.

Aim: To evaluate the hepatic expression of the intrahepatic Tregs, Ig (immunoglobulin) G and IgM plasma cells in autoimmune hepatitis (AIH) and other chronic liver diseases (CLDs).

Material and methods: This study included 100 pediatric patients; 50 AIH and 50 CLDs other than AIH. All patients were subjected to routine investigations of CLDs plus immune-staining of liver tissue for FOXp3, IgG and IgM plasma cells, CD4 and CD8 T-cells.

Results: The FOXP3+ T cells in patients with AIH (6.3 ± 5) were significantly higher than that in the non-AIH (2.1 ± 2.6). FOXP3+ T cells were abundant in liver tissue with marked inflammatory cellular infiltrate. CD4+ and CD8+ infiltrating the liver tissue and IgG positive cells were significantly higher in AIH group, while the expression of IgM positive cells showed no significant difference. The IgG/IgM was significantly higher in the AIH treatment responders (3 ± 3) than non-responders (1.6 ± 0.5), while there was no significant difference regarding the intrahepatic expression of FOXP3+, CD4+, CD8+ cells, T-cells, IgG and IgM plasma cells.

Conclusion: Intrahepatic Tregs were increased in number in patients with AIH in the initial presentation, and their presence is associated with increased activity and inflammation in liver biopsy.

MeSH terms

  • Age Factors
  • Anti-Inflammatory Agents / therapeutic use
  • Biomarkers / analysis
  • Biopsy
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / analysis
  • Hepatitis, Autoimmune / drug therapy
  • Hepatitis, Autoimmune / immunology*
  • Hepatitis, Autoimmune / pathology
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / immunology*
  • Liver / pathology
  • Male
  • Plasma Cells / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunoglobulin G
  • Immunoglobulin M