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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Bibliographic Details
Published in:	PLoS pathogens Vol. 8; no. 9; p. e1002913
Main Authors:	Boettler, Tobias, Moeckel, Friedrich, Cheng, Yang, Heeg, Maximilian, Salek-Ardakani, Shahram, Crotty, Shane, Croft, Michael, von Herrath, Matthias G.
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.09.2012 Public Library of Science (PLoS)
Subjects:	Acute Disease Adaptive Immunity - genetics Animals Antibodies Antiviral agents Biology CD134 antigen CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Chlorocebus aethiops Chronic infection Data processing Development and progression Germinal Center - metabolism Germinal Center - physiology Germinal centers Health aspects Immune system Immunological memory Immunology Infections Lymphocyte Activation - genetics Lymphocyte Activation - immunology Lymphocytes T Lymphocytic Choriomeningitis - genetics Lymphocytic Choriomeningitis - immunology Lymphocytic Choriomeningitis - prevention & control Lymphocytic choriomeningitis virus - immunology Lymphocytic choriomeningitis virus - physiology Medicine Memory cells Mice Mice, Inbred C57BL Mice, Knockout Pathogens PD-1 protein Persistent infection Physiological aspects Receptors, OX40 - genetics Receptors, OX40 - metabolism Receptors, OX40 - physiology Replication Signal transduction Spreading T cell receptors T cells Tumor necrosis factor Vero Cells Viral infections Virulence (Microbiology) Virus diseases Virus Diseases - genetics Virus Diseases - immunology Virus Diseases - prevention & control Virus Latency - immunology Virus Latency - physiology Germany
ISSN:	1553-7374, 1553-7366, 1553-7374
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 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