Quantification and localisation of FOXP3+ T lymphocytes and relation to hepatic inflammation during chronic HCV infection.
OBJECTIVE
T lymphocyte-mediated immune reactions are closely involved in the pathogenesis of HCV-induced chronic liver disease. Regulatory T cells are able to suppress HCV-specific T lymphocyte proliferation and cytokine secretion during chronic HCV infection. We wished to address to what extent regulatory T cells exist in the livers of HCV+ individuals, and what the role of such cells might be in disease progression.


METHODS
We analysed the frequency and distribution of FOXP3+ cells, along with CD4, CD8 and CD20+ cells, in liver biopsies of 28 patients with chronic HCV and 14 patients with PBC, and correlated these data with histological parameters.


RESULTS
A striking number of FOXP3+ cells were present in the portal tract infiltrates of HCV-infected livers. FOXP3+ cells were largely CD4+ and there was a remarkably consistent ratio of total CD4+:FOXP3+ cells in liver across a wide range of disease states of around 2:1. This differed substantially from the ratio observed in PBC (10:1, P=0.001).


CONCLUSIONS
An unexpectedly high proportion of the cellular infiltrate in persistent HCV infection comprises FOXP3+ cells. The relative proportion of FOXP3+ cells remains similar in both mild and severe fibrosis. These cells are likely to play a critical role in intrahepatic immune regulation, although their overall role in disease progression remains to be determined.
Ward
Scott M
SM
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, South Parks Road, Oxford, UK.
Fox
Bridget C
BC
Brown
Philip J
PJ
Worthington
Joy
J
Fox
Stephen B
SB
Chapman
Roger W
RW
Fleming
Kenneth A
KA
Banham
Alison H
AH
Klenerman
Paul
P
D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000473:pathology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors