CD4+Foxp3+ T cells promote aberrant immunoglobulin G production and maintain CD8+ T‐cell suppression during chronic liver disease. Issue 2 (19th December 2016)

• Record Type: Journal Article
• Authors: Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev; Elrod, Elizabeth J.; Rahman, Khalidur; Ibegbu, Chris C.; Magliocca, Joseph F.; Adams, Andrew B.; Anania, Frank; Grakoui, Arash
• Is Part Of: Hepatology. Volume 65:Issue 2(2017)
• Page Start: 661
• Page End: 677
• Publication Date: 2016-12-19
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.28894
• Languages: English
• ISSNs: 0270-9139

Abstract

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;65:661‐677).