An OX40/OX40L interaction directs successful immunity to hepatitis B virus
| Autor: | Amanda Goodsell, Ugur Halac, Joyce Judge, Jody L. Baron, Lia Avanesyan, Keith Mansfield, Stewart Cooper, Eric Pai, Michael Croft, Philip J. Rosenthal, Stephen L. Nishimura, Meghan Holdorf, Adil E. Wakil, Arya Koshti, Jillian M. Jespersen, Jean Publicover, Audra J. Johnson, Anuj Gaggar |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.disease_cause Medical and Health Sciences Hepatitis Mice 0302 clinical medicine Receptors Innate 2.1 Biological and endogenous factors OX40 Chronic Aetiology Liver injury Mice Knockout Liver Disease General Medicine Biological Sciences Hepatitis B Infectious Diseases medicine.anatomical_structure 030211 gastroenterology & hepatology Infection Hepatitis B virus Knockout T cell Chronic Liver Disease and Cirrhosis OX40 Ligand Article Hepatitis - B 03 medical and health sciences Immune system Hepatitis B Chronic Antigen Immunity medicine Humans Animals Innate immune system business.industry Inflammatory and immune system Receptors OX40 medicine.disease Immunity Innate Good Health and Well Being 030104 developmental biology Immunology Digestive Diseases business |
| Zdroj: | Science translational medicine, vol 10, iss 433 |
| ISSN: | 1946-6242 |
| Popis: | Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB. |
| Databáze: | OpenAIRE |
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