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CD4 + Foxp3 + T cells promote aberrant immunoglobulin G production and maintain CD8 + T‐cell suppression during chronic liver disease
Author(s) -
Tedesco Dana,
Thapa Manoj,
Gumber Sanjeev,
Elrod Elizabeth J.,
Rahman Khalidur,
Ibegbu Chris C.,
Magliocca Joseph F.,
Adams Andrew B.,
Anania Frank,
Grakoui Arash
Publication year - 2017
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28894
Subject(s) - immunology , foxp3 , cd8 , population , biology , t cell , liver disease , antibody , cytotoxic t cell , cd40 , liver injury , immune system , medicine , endocrinology , in vitro , biochemistry , environmental health
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. (H epatology 2017;65:661‐677).