title: TIPE2 protein negatively regulates HBV-specific CD8⁺ T lymphocyte functions in humans.
abstract: Cytotoxic T cell-mediated killing of virus-infected hepatocytes is an important pathogenic process of hepatitis B. However, its underlying molecular mechanisms are not fully understood. TNFAIP8L2 (TIPE2) is a newly described anti-inflammatory protein that is essential for maintaining immune homeostasis. In this study, we found that the protein levels of TIPE2 in PBMCs of hepatitis B patients were significantly reduced and negatively correlated with the sera values of aminotransferases. Importantly, TIPE2 protein was downregulated preferentially in cytotoxic CD8(+) T cells, not CD4(+) helper T cells. The CD8(+) T cells with low TIPE2 expression were more activated and produced higher levels of perforin, granzyme B, and IFN-γ. As a result, their cytolytic activity was markedly enhanced. Interestingly, HBc18-27 peptide stimulation could reduce TIPE2 expression in PBMCs. These results indicate that TIPE2 plays an important role in regulating HBV-specific CD8(+) T cell functions in patients with hepatitis B.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatology, Province Hospital of Shandong University, Ji'nan, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University, Ji'nan, PR China.
authors.forename: Lianying
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Ji'nan, PR China. Electronic address: suxiasd@163.com.
authors.forename: Suxia
authors.initials: S
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D013045:Species Specificity; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C552057:TNFAIP8L2 protein, human; D054353:Perforin; D007371:Interferon-gamma
keywords: CD8(+) T; Cellular immunity; Hepatitis B virus; Inflammation; TNFAIP8L2 (TIPE2)