OX40 Facilitates Control of a Persistent Virus Infection

During acute viral infections, clearance of the pathogen is followed by the contraction of the anti-viral T cell compartment. In contrast, T cell responses need to be maintained over a longer period of time during chronic viral infections in order to control viral replication and to avoid viral spre...

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Vydáno v:PLoS pathogens Ročník 8; číslo 9; s. e1002913
Hlavní autoři: Boettler, Tobias, Moeckel, Friedrich, Cheng, Yang, Heeg, Maximilian, Salek-Ardakani, Shahram, Crotty, Shane, Croft, Michael, von Herrath, Matthias G.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 01.09.2012
Public Library of Science (PLoS)
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ISSN:1553-7374, 1553-7366, 1553-7374
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Shrnutí:During acute viral infections, clearance of the pathogen is followed by the contraction of the anti-viral T cell compartment. In contrast, T cell responses need to be maintained over a longer period of time during chronic viral infections in order to control viral replication and to avoid viral spreading. Much is known about inhibitory signals such as through PD-1 that limit T cell activity during chronic viral infection, but little is known about the stimulatory signals that allow maintenance of anti-viral T cells. Here, we show that the co-stimulatory molecule OX40 (CD134) is critically required in the context of persistent LCMV clone 13 infection. Anti-viral T cells express high levels of OX40 in the presence of their cognate antigen and T cells lacking the OX40 receptor fail to accumulate sufficiently. Moreover, the emergence of T cell dependent germinal center responses and LCMV-specific antibodies are severely impaired. Consequently, OX40-deficient mice fail to control LCMV clone 13 infection over time, highlighting the importance of this signaling pathway during persistent viral infection.
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Conceived and designed the experiments: TB FM SSA SC MC MvH. Performed the experiments: TB FM YC MH. Analyzed the data: TB FM. Contributed reagents/materials/analysis tools: SSA SC MC. Wrote the paper: TB FM MC SC MvH.
Current address: University Hospital Freiburg, Department of Gastroenterology and Hepatology, Freiburg, Germany.
The authors have declared that no competing interests exist.
Current address: University College London, Division of Infection and Immunity, London, Great Britain.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002913