AASLD2014:PD-1，CTLA-4和Foxp3表达的替诺福韦治疗慢性乙型肝炎过

StephenW

1735
Phenotypic Characteristics of PD-1, CTLA-4 and FoxP3 Expression during Tenofovir therapy in Chronic Hepatitis B
Hyosun Cho1, Chang Wook Kim2, Yu seung Kim2, Hee Yeon Kim2, Jong Young Choi2, Seung Kew Yoon2, Chang Don Lee3;
1Pharmacy, Duksung Women's University, Seoul, Republic of Korea; 2Internal Medicine, The Catholic University of Korea, Uijeonbu-shi, Republic of Korea; 3Internal Medicine, International St. Mary's Hospital, Incheon, Republic of Korea

Background: Inhibitory molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with antiviral effector T-cell dysfunction, which influences on T-cell exhaustion and persistent viral infection. These PD-1 and CTLA-4 are up-regulated in chronic viral infection such as chronic hepatitis C, chronic hepatitis B and human immunodeficiency virus infection but there is few report about the role of PD-1 and CTLA-4 in patients with chronic hepatitis B during antiviral therapy with tenofovir. We investigated the expression of PD-1 and CTLA-4 during tenofovir treatment in patients with chronic hepatitis B. Methods: Nine patients with chronic hepatitis B under tenofovir treatment were enrolled for detection of intrinsic inhibitory molecules of T cell signals (PD-1, CTLA-4) and extrinsic inhibitory molecule, FoxP3. Peripheral blood mononuclear cells (PBMC) were isolated from these subjects before tenofovir treatment (T0) and 1 month (T1), 3 month (T3), 6 month (T6) during tenofovir treatment. The expressions of PD-1, CTLA-4 and FoxP3 on T cells were monitored by flow cytometry. Results: T cells from patients with chronic hepatitis B under tenofovir treatment showed decreased expression of PD-1, CTLA-4, and FoxP3 at T6 compared to T0 (%PD-1/ CD8, 5.0 ± 2.2 vs. 4.0 ± 1.2; %CTLA-4/CD8, 1.7 ± 0.9 vs. 1.2 ± 0.6; %FoxP3/CD4, 7 ± 2.5 vs. 6.1 ± 2.6 showed as mean ± SD). During the initial phase of tenofovir treatment, FoxP3 and PD-1 fluctuate at T1 and T3 but, CTLA-4 decreased steadily even at T1 and T3. Conclusions: In chronic hepatitis B, PD-1 and CTLA-4 as inhibitory T cell molecules and FoxP3 as regulatory T cell marker are down-regulated during initial 6 month tenofovir therapy, which could restore HBV-specific T cell function during tenofovir antiviral therapy. Long-term effects of tenofovir on host immune system are needed to be elucidate.

Disclosures:

Chang Wook Kim - Consulting: Gilead, MSD; Grant/Research Support: BMS, Handok, Pharmicell, Pharmaking; Speaking and Teaching: BMS, Donga, Dae-woong

The following people have nothing to disclose: Hyosun Cho, Yu seung Kim, Hee Yeon Kim, Jong Young Choi, Seung Kew Yoon, Chang Don Lee

StephenW

1735
PD-1，CTLA-4和Foxp3表达的替诺福韦治疗慢性乙型肝炎过程中的表型特征
Hyosun Cho1，昌旭Kim2，俞胜Kim2，熙妍Kim2，钟扬Choi2，承邱Yoon2，张唐Lee3;
1Pharmacy，Duksung女子大学，首尔，韩国; 2Internal医学，韩国天主教大学，Uijeonbu市，大韩民国; 3Internal医学，国际圣玛丽医院，仁川，韩国

背景：阻抑分子，例如程序性死亡-1（PD-1）和细胞毒性T淋巴细胞相关抗原4（CTLA-4），具有抗病毒效应T细胞功能异常，从而影响对T细胞耗竭和持久性病毒感染有关。这些PD-1和CTLA-4的上调在慢性病毒感染，例如慢性丙型肝炎，慢性乙型肝炎和人类免疫缺陷病毒感染，但有大约PD-1和CTLA-4在慢性乙型肝炎患者中的作用很少报告在抗病毒治疗与替诺福韦乙肝。我们在治疗慢性乙型肝炎的研究方法的PD-1和CTLA-4的表达过程中替诺福韦治疗方法：9例慢性乙型肝炎患者在替诺福韦治疗被纳入检测T细胞信号固有的抑制分子（PD-1， CTLA-4）和外在抑制分子，FoxP3的。外周血单个核细胞（PBMC），在替诺福韦治疗（T0）和1月（T1），3月（T3），6个月（T6）之前，这些科目中替诺福韦治疗中分离得到。 PD-1，CTLA-4和FoxP3的T细胞上的表达通过流式细胞术监测。结果：T细胞，从患者的下诺福韦治疗慢性乙型肝炎的显示相比T0降低PD-1，CTLA-4和Foxp3的表达在T6（％PD-1/ CD8，5.0±2.2与4.0±1.2;％ CTLA-4/ CD8 +，1.7±0.9与1.2±0.6;％的FoxP3/ CD4 +，7±2.5与6.1±2.6均数±标准差）。在替诺福韦治疗的FoxP3和PD-1的初始相位波动在T1和T3但是，CTLA-4，即使在​​T1和T3稳步下降。结论：在慢性乙型肝炎，PD-1和CTLA-4的抑制性T细胞的分子和FoxP3的作为调节性T细胞标志物是在初始6个月诺福韦治疗，这可能在诺福韦抗病毒治疗恢复HBV特异性T细胞功能下调。需要替诺福韦对宿主免疫系统的长期影响要澄清。

披露：

昌旭金 - 咨询：Gilead公司，MSD;格兰特/研究支持：BMS，Handok，Pharmicell，Pharmaking;口语和教学：BMS，东阿，大亚雄

下面的人都没有透露：Hyosun町，宇胜金熙妍金，钟杨财，胜邱尹，张唐李