CD4+ Foxp3+ T cells promote aberrant immunoglobulin G production and maintain CD8+ T-cell suppression during chronic liver disease.
Hepatology
; 65(2): 661-677, 2017 02.
Article
in En
| MEDLINE
| ID: mdl-27774611
ABSTRACT
Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8+ T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4+ T-cell help. Elevated CD4+ forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8+ T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4+ Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4+ Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. CONCLUSION:
Liver disease elicits alterations in the intrahepatic CD4+ T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65661-677).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin G
/
CD8-Positive T-Lymphocytes
/
Forkhead Transcription Factors
/
Liver Cirrhosis
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Hepatology
Year:
2017
Document type:
Article
Affiliation country:
Gabon