Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses.
Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses.
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DOI：
10.1016/j.vaccine.2011.02.052
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发表时间：
2011-04-12
期刊：
影响因子：
5.5
通讯作者：
Yao, Zhi Q.
中科院分区：
文献类型：
--
作者：
Moorman, Jonathan P.;Zhang, Chun L.;Ni, Lei;Ma, Cheng J.;Zhang, Ying;Wu, Xiao Y.;Thayer, Penny;Islam, Tareq M.;Borthwick, Thomas;Yao, Zhi Q.
建议在丙型肝炎病毒(丙型肝炎病毒)感染的情况下接种乙肝病毒疫苗，但与未感染的人群相比，接种疫苗的反应迟钝。丙型肝炎病毒感染者免疫反应失败的机制尚不清楚，但被认为是慢性病毒感染期间淋巴细胞功能障碍的结果。我们最近证实，PD-1是一种新的T细胞受体(TCR)信号的负性免疫调节剂，参与了慢性丙型肝炎病毒感染时T和B淋巴细胞的失调。在这份报告中，我们进一步研究了PD-1通路在调节丙型肝炎病毒感染者接种乙肝疫苗后的CD4+T细胞反应中的作用。在未来的丙型肝炎病毒感染队列中，通过血清转换检测，丙型肝炎病毒感染者对乙肝疫苗的应答率较低(53%)，而在健康或自发丙型肝炎病毒消退的个体中观察到较高的应答率(94%)。与接受过一系列乙肝疫苗免疫的丙型肝炎病毒感染者相比，无应答者对抗CD3/CD28抗体或乙肝表面抗原(HBs)的体外刺激的CD4+T细胞应答较低。在这些乙肝疫苗无应答者中，检测到CD4+T细胞上PD-1的表达水平相对高于应答者，这与细胞激活状态呈负相关。重要的是，阻断PD-1通路改善了对体外乙肝表面抗原或抗CD3/CD28刺激的T细胞的激活和增殖。这些结果提示，PD-1信号通路可能参与了丙型肝炎病毒感染者对乙肝疫苗免疫应答的受损，阻断这一负信号通路可能提高慢性病毒感染的免疫成功率。
Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus (HCV) infection is recommended, but responses to vaccination are blunted when compared to uninfected populations. The mechanism for this failure of immune response in HCV-infected subjects remains unknown but is thought to be a result of lymphocyte dysfunction during chronic viral infection. We have recently demonstrated that PD-1, a novel negative immunomodulator for T cell receptor (TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic HCV infection. In this report, we further investigated the role of the PD-1 pathway in regulation of CD4+ T cell responses to HBV vaccination in HCV-infected individuals. In a prospective HCV infected cohort, a poor response rate to HBV vaccination as assayed by seroconversion was observed in HCV-infected subjects (53%), while a high response rate was observed in healthy or spontaneously HCV-resolved individuals (94%). CD4+ T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. PD-1 expression on CD4+ T cells were detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. These results suggest that PD-1 signaling may be involved in impairing CD4+ T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection.
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