title: CD4+Foxp3+T cells promote aberrant immunoglobulin G production and maintain CD8+T-cell suppression during chronic liver disease.
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.
  
  
  
  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;65:661-677).
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
authors: Dana
authors: D
authors: Tedesco
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
authors: Manoj
authors: M
authors: Thapa
authors: Division of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors: Sanjeev
authors: S
authors: Gumber
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
authors: Elizabeth J
authors: EJ
authors: Elrod
authors: Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA.
authors: Khalidur
authors: K
authors: Rahman
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
authors: Chris C
authors: CC
authors: Ibegbu
authors: Department of Surgery, Emory University School of Medicine, Atlanta, GA.
authors: Joseph F
authors: JF
authors: Magliocca
authors: Department of Surgery, Emory University School of Medicine, Atlanta, GA.
authors: Andrew B
authors: AB
authors: Adams
authors: Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA.
authors: Frank
authors: F
authors: Anania
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.|Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA.
authors: Arash
authors: A
authors: Grakoui
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000473:pathology; D022781:Hepatocytes; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; D007074:Immunoglobulin G