B and T lymphocyte attenuator is highly expressed on intrahepatic T cells during chronic HBV infection and regulates their function
| Autor: | Lei Li, Beiying Wu, Qian Shen, Xiaomeng Nie, Huaizhou Wang, Cen Jiang, Liang Hu, Xuefeng Wang, Gang Cai, Jiafei Lin |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male T-Lymphocytes T cell Programmed Cell Death 1 Receptor BTLA Biology Interferon-gamma Young Adult Hepatitis B Chronic Antigen Interferon medicine Humans Cytotoxic T cell Receptors Immunologic Aged Gastroenterology Cell Differentiation Dendritic Cells T lymphocyte Middle Aged Flow Cytometry Up-Regulation medicine.anatomical_structure T cell differentiation Immunology Leukocytes Mononuclear Interleukin-2 Female Cytokine secretion medicine.drug |
| Zdroj: | Journal of Gastroenterology. 48:1362-1372 |
| ISSN: | 1435-5922 0944-1174 |
| DOI: | 10.1007/s00535-013-0762-9 |
| Popis: | T cell antiviral function is impaired during chronic hepatitis B (CHB). Programmed death-1 (PD-1) impairs antiviral T cell responses, but dysfunction is not always reversed by blockade of PD-1 pathway. Whether distinct T cell populations expressing different sets of inhibitory molecules exist has not been determined. We studied the expression of the B and T lymphocyte attenuator (BTLA) on both peripheral blood mononuclear cells (PBMC) and intrahepatic lymphocytes, and the effects of blocking BTLA on circulating and intrahepatic T cells in CHB patients. Sixty-three CHB patients who underwent liver biopsy were enrolled. The expression of BTLA and PD-1 on PBMC and intrahepatic T cells was assessed by flow cytometry with antibodies to T cell differentiation molecules. Functional recovery was evaluated by analyzing production of interferon (IFN)-γ and interleukin (IL)-2 after incubation of T cells with anti-CD3 and irradiated mature dendritic cells in the presence of anti-BTLA, anti-PD-1, or both. Intrahepatic T cells expressed higher levels of BTLA than their peripheral counterparts. A significant fraction of intrahepatic T cells coexpressed BTLA and PD-1 and showed deep exhaustion of T cell responses. Blockade of the BTLA pathway enhanced both intrahepatic and PBMC T cell proliferation and cytokine secretion, and exhibited an additive effect upon blockage of PD-1. Upregulation of inhibitory receptor BTLA restricts T cell responses in CHB. T cell exhaustion by high antigen concentrations exacerbates dysfunction of peripheral and intrahepatic T cells. Blockage of BTLA is a potential therapeutic approach for chronic HBV infection that may act by restoring antiviral T cell responses. |
| Databáze: | OpenAIRE |
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