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- Title
IL-35 inhibits HBV antigen-specific IFN-γ-producing CTLs in vitro.
- Authors
Xuefen Li; Li Tian; Yuejiao Dong; Qiaoyun Zhu; Yiyin Wang; Wenzheng Han; Xia Liu; Qin Ni; Yu Chen; Lanjuan Li
- Abstract
Interleukin-35 is an inhibitory cytokine consisting of Interleukin-12A and Epstein-Barr virus-induced gene 3 and is required by regulatory T-cells for maximal activity. During chronic hepatitis B virus (HBV) infection, regulatory T-cells have immunosuppressive effects on HBV-specific T helper cells, yet little is known about the complex regulation of regulatory T-cells and their contribution to the inadequate immune system response to the virus. In this study, we investigatedwhether interleukin-35 is involved in HBV-related cellular immune responses. CD4+ T-cells from peripheral blood were derived from healthy volunteers, resolved HBV individuals and chronic active hepatitis B patients and stimulated with CD3/28-conjugated beads. We analyzed mRNA and protein levels of interleukin-35, and assessed the inhibitory effect of interleukin-35 on HBV core antigen specific cytotoxic T lymphocytes, dendritic cells, and effector T-cells. Correlation analyses between liver inflammation and HBV DNA load were conducted. Results show thatchronic HBV patients harbor significantly higher levels of Epstein-Barr virus-induced gene 3 mRNA and protein in CD4+ T-cells compared to healthy volunteers and resolved HBV individuals. Interleukin-35 suppressed the proliferation of HBVantigen-specific cytotoxic T-lymphocytes and interferon-? production in vitro. Ex vivo, interleukin-35 decreased the proliferation of CD4+CD45RA+ naïve T-cells, especially in CD4+CD25-CD45RA+ naïve effector T-cells. Interleukin-35 inhibited the expansion of CD11c+ dendritic cells. Ourdata indicate that interleukin-35 is highly expressed in chronic HBV CD4+ T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV.
- Subjects
HEPATITIS B virus; EPSTEIN-Barr virus genetics; CYTOTOXIC T cells; INTERLEUKINS; IMMUNOSUPPRESSION; STATISTICAL correlation; IMMUNE response
- Publication
Clinical Science, 2015, Vol 129, Issue 5, p395
- ISSN
0143-5221
- Publication type
Article
- DOI
10.1042/CS20140511