HCV+ hepatocytes induce human regulatory CD4+ T cells through the production of TGF-beta.
HCV+ hepatocytes induce human regulatory CD4+ T cells through the production of TGF-beta.
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DOI：
10.1371/journal.pone.0012154
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发表时间：
2010-08-13
期刊：
影响因子：
3.7
通讯作者：
Hahn YS
中科院分区：
文献类型：
--
作者：
Hall CH;Kassel R;Tacke RS;Hahn YS
Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4+ regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4+ T cells. The production of IFN-γ was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4+ T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV+ hepatocytes upregulated the production of TGF-β and blockade of TGF-β abrogated Treg phenotype and function. These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses.
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