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
em 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).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Linfócitos T CD8-Positivos
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Fatores de Transcrição Forkhead
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Cirrose Hepática
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Gabão