title: Hepatic expansion of virus-specific CD8+BTLA+T cells with regulatory properties in chronic hepatitis B virus infection.
abstract: Similar to programmed death-1 (PD-1), B and T lymphocyte attenuator (BTLA) is a co-inhibitory molecule of the CD28 family. PD-1 is involved in T cell exhaustion during chronic viral infection. However, the role of BTLA in virus-specific T cells is poorly defined. Here we investigated the expression and function of BTLA in T cells from patients with chronic hepatitis B virus (HBV) infection. The phenotype of peripheral and intrahepatic HBV-specific T cells from 43 patients with chronic HBV infection was assessed by flow cytometry. Functional evaluation was analyzed by T cell expansion and cytokine secretion after different treatments. In chronic HBV patients, a subset of inefficient interferon-γ producing antigen-specific CD8+T cells recruited to the liver expressed high BTLA levels. The BTLA+HBV-specific CD8+T cell suppressive function was antigen-specific, at least in the induction phase, because they were only activated by a pool of HBV peptides but not with a pool of unrelated peptides. Suppression of T cell responses was restored by a BTLA signaling blockade and neutralizing IL-10, indicating that BTLA signaling-mediated IL-10 secretion plays a key role in suppression. This study provides important evidence that there is a subset of liver infiltrated virus-specific CD8+BTLA+regulatory T cells in patients with chronic HBV infection. This subset of cells plays a pivotal role in controlling hepatic effector CD8+T cell responses through BTLA signaling mediated regulatory factor IL-10 production.
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China; Department of Experimental Diagnosis, Changhai Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: Huaizhou
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
authors.forename: Beiying
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Clinical Pathology, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
authors.forename: Jiafei
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
authors.forename: Cen
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China. Electronic address: caigangsmmu@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Experimental Diagnosis, Changhai Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C488868:BTLA protein, mouse; D016207:Cytokines; D011971:Receptors, Immunologic; D016753:Interleukin-10
keywords: B and T lymphocyte attenuator; Chronic virus infection; Hepatitis B virus; Regulatory CD8(+) T cells