IL-35 inhibits HBV antigen-specific IFN-γ-producing CTLs in vitro

2015 ◽  
Vol 129 (5) ◽  
pp. 395-404 ◽  
Author(s):  
Xuefen Li ◽  
Li Tian ◽  
Yuejiao Dong ◽  
Qiaoyun Zhu ◽  
Yiyin Wang ◽  
...  

Inhibitory cytokine, interleukin-35 (IL-35), is highly expressed in CD4+ T-cells from CHB patients and plays an important role in the inhibition of the cellular immune response, which contribute to the development and progression of chronic hepatitis B.

2011 ◽  
Vol 91 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Yu Chen ◽  
Xuefen Li ◽  
Bo Ye ◽  
Xianzhi Yang ◽  
Wei Wu ◽  
...  

2019 ◽  
Vol 133 (17) ◽  
pp. 1917-1934
Author(s):  
Madhuparna Nandi ◽  
Sourina Pal ◽  
Sumantra Ghosh ◽  
Bidhan Chandra Chakraborty ◽  
Debangana Dey ◽  
...  

Abstract During chronic hepatitis B (CHB), CD8+ T cells down-regulate CD28, the primary co-stimulation molecule for T-cell activation. Diverse functional attributes of CD8+CD28− T cells are suggested in various disease contexts. The present study aimed to characterize CD8+CD28− T cells in different phases of chronic Hepatitis B virus (HBV) infection (CHI)- Immune-tolerance (IT), Hepatitis B e-antigen-positive CHB (EP-CHB), Inactive carriers (IC) and Hepatitis B e-antigen-negative CHB (EN-CHB), to appraise their contribution in HBV-related disease pathophysiology. Flow cytometry analysis of T cells in peripheral blood of study subjects revealed enhanced CD8+CD28− T-cell accumulation in EP-/EN-CHB, compared with IT/IC and they expanded equivalently in HBV-specific and non-specific CD8+ T-cell compartments. Profound increase in CD8+CD28− T cells expressing perforin/granzyme-B/CD57/IFN-γ/TNF-α and markers of terminal differentiation were observed exclusively in EP-/EN-CHB. Further, activation with anti-NKG2D resulted in heightened IFN-γ/TNF-α production selectively from CD8+CD28− T cells, suggesting NKG2D-mediated alternative co-stimulation. CD8+CD28− T cells sorted from CHB patients induced enhanced apoptosis of peripheral blood mononuclear cells (PBMC), including CD4+ T cells. However, NKG2D-ligand (major histocompatibility complex class I chain-related molecule A/B (MICA/B)) was preferentially expressed by HBV-specific CD4+ T cells of CHB patients, making these cells a potential target to NKG2D-dependent CD8+CD28− T-cell killing. Both CD28+ and CD28− T cells in CHB expressed CXCR3 at similar levels and thus capable of homing to the liver. A positive correlation was seen between CD8+CD28− T-cell frequency and serum-alanine transaminase (ALT) levels and CHB-derived CD8+CD28− T cells caused pronounced cell death in HBV-transfected Huh7 cells. Immunofluorescence staining identified greater intrahepatic incidence of CD8+CD28− T cells but decline in CD4+ T cells in CHB than IC. Collectively, CD8+CD28− T cells demonstrated differential distribution and phenotypic/functional skewing in different CHI phases and contribute to disease progression by Perforin-Granzyme- or IFN-γ-TNF-α-mediated cytotoxicity while restraining antiviral immunity through NKG2D-dependent HBV-specific CD4+ T-cell depletion.


2002 ◽  
Vol 36 ◽  
pp. 222
Author(s):  
John Elefsiniotis ◽  
Ioannis Papanikolaou ◽  
Irene Glynou ◽  
Margarita Simou ◽  
Despoina Papadeli ◽  
...  

2017 ◽  
Vol 41 (2) ◽  
pp. 423-438 ◽  
Author(s):  
Quanhui Tan ◽  
Siyuan Ma ◽  
Jianjun Hu ◽  
Xiaohua Chen ◽  
Yongsheng Yu ◽  
...  

Background: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved. Methods: In this study, recombinant adenoviral vectors harboring the hepatitis B core antigen (HBcAg) and the TPPII gene were constructed (Adv-HBcAg and Adv-HBcAg-TPPII), and H-2Kd HBV-transgenic BALB/c mice and HLA-A2 C57BL/6 mice were immunized with these vectors, respectively. We evaluated the specific immune responses induced by Adv-HBcAg-TPPII in the HBV transgenic BALB/c mice and HLA-A2 C57BL/6 mice as well as the anti-viral ability of HBV transgenic mice, and we explored the underlying mechanisms. Results: We found that immunization with Adv-HBcAg-TPPII induced the secretion of the cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as well as the activities of IFN-γ-secreting CD8+ T cells and CD4+ T cells. In addition, HBcAg-specific CTL activity in C57/BL mice and HBV transgenic animals was significantly enhanced in the Adv-HBcAg-TPPII group. Furthermore, Adv-HBcAg-TPPII decreased the hepatitis B surface antigen (HBsAg) and HBV DNA levels and the amount of HBsAg and HBcAg in liver tissues. Moreover, Adv-HBcAg-TPPII enhanced the expression of T-box transcription factor (T-bet) and downregulated GATA-binding protein 3 (GATA-3) while increasing the expression levels of JAK2, STAT1, STAT4 and Tyk2. Conclusions: These results suggested that the JAK/STAT signaling pathway participates in the CTL response that is mediated by the adenoviral vector encoding TPPII. Adv-HBcAg-TPPII could therefore break immune tolerance and stimulate HBV-specific cytotoxic T lymphocyte activity and could have a good therapeutic effect in transgenic mice.


2014 ◽  
Vol 11 (2) ◽  
pp. 1284-1291 ◽  
Author(s):  
GUANGCHENG LUO ◽  
XIA FENG ◽  
YANXIANG HUANG ◽  
TINGTING YI ◽  
DONGSHENG WANG ◽  
...  

2017 ◽  
Vol 3 (2) ◽  
pp. 28
Author(s):  
Desie Dwi Wisudanti

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.


2014 ◽  
Vol 27 (4) ◽  
pp. 775 ◽  
Author(s):  
AbeerA El-Gazzar ◽  
MahaA El-Basuoni ◽  
MohamedA Soliman ◽  
HassanE Zaghla ◽  
MahaM Allam

2011 ◽  
Vol 139 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Fen Liu ◽  
Fuyi Tong ◽  
Yan He ◽  
Haiyan Liu

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