目的：剖析干扰素 α (IFN-α) 介导的 T 细胞重塑的潜在机制对于实现慢性乙型肝炎 (CHB) 患者的最佳治疗反应是必不可少的。然而，在这个过程中对 B 细胞知之甚少。本研究旨在阐明 B 细胞在 IFN-α 介导的抗乙型肝炎病毒 (HBV) 细胞免疫中的作用。
方法：在 B 细胞缺陷小鼠模型中研究 B 细胞对 IFN-α 介导的 T 细胞反应的影响，并通过 HBV 和 IFN-α 质粒流体动力学注射。进行单细胞 RNA 测序以剖析 B 细胞和 T 细胞亚群之间的串扰以及来自 IFN-α 治疗的 CHB 患者的纵向血液样本的潜在分子和途径特征。
结果：B 细胞耗竭损害了功能性 T 细胞亚群，包括 HBV 特异性 CD8+ T 细胞，并导致 HBV 清除延迟。 IFN-α 治疗增强了 HBV 特异性 CD8+ T 细胞的反应，而这种作用在 B 细胞缺陷小鼠中消失了。潜在机制与 IFN-α 增强的 B 细胞与 T 细胞的连接有关，这是由 B 细胞中的抗原呈递和共刺激功能介导的。
Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner
Shihong Zhong 1 , Qiong Li 1 , Chunhua Wen 1 , Yifan Li 1 , Yang Zhou 1 , Zihan Jin 1 , Guofu Ye 1 , Yanda Zhao 2 , Jinlin Hou 3 , Yongyin Li 4 , Libo Tang 5
Affiliations
Affiliations
1
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2
School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
3
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
4
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
5
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
Objectives: Dissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity.
Method: The effects of B cells on IFN-α-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-α plasmid hydrodynamic injection. Single-cell RNA sequencing was performed to dissect the crosstalk among B cell and T cell subsets and the underlying molecule and pathway signatures on longitudinal blood samples from IFN-α-treated CHB patients.
Results: B cell depletion impaired the functional T cell subsets, including HBV-specific CD8+ T cells, and engendered a delayed HBV clearance. IFN-α treatment boosted the response of HBV-specific CD8+ T cells, whereas such effects disappeared in B cell-deficient mice. The underlying mechanisms were associated with IFN-α-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells.
Conclusion: IFN-α orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.
Keywords: B cell; Cellular immunity; Hepatitis B virus; IFN-α; T cell.
Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.