Abstract：
: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.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Publicover J,Gaggar A,Jespersen JM,Halac U,Johnson AJ,Goodsell A,Avanesyan L,Nishimura SL,Holdorf M,Mansfield KG,Judge JB,Koshti A,Croft M,Wakil AE,Rosenthal P,Pai E,Cooper S,Baron JLdoi
10.1126/scitranslmed.aah5766subject
Has Abstractpub_date
2018-03-21 00:00:00issue
433eissn
1946-6234issn
1946-6242pii
10/433/eaah5766journal_volume
10pub_type
杂志文章abstract：:Research standards deviate in genetic versus nongenetic epidemiology. Besides some immutable differences, such as the correlation pattern between variables, these divergent research standards can converge considerably. Current research designs that dissociate genetic and nongenetic measurements are reaching their limi...
journal_title：Science translational medicine
pub_type： 杂志文章
doi：10.1126/scitranslmed.3000247
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pub_type： 临床试验,杂志文章
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pub_type： 评论,杂志文章
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journal_title：Science translational medicine
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更新日期：2019-06-05 00:00:00
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更新日期：2019-09-18 00:00:00
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doi：10.1126/scitranslmed.aaf3962
更新日期：2017-05-24 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2017-12-06 00:00:00
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更新日期：2020-11-11 00:00:00
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pub_type： 杂志文章
doi：10.1126/scitranslmed.3004474
更新日期：2012-11-07 00:00:00
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pub_type： 评论,杂志文章
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