title: OX40 facilitates control of a persistent virus infection.
abstract: 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.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Tobias
authors.initials: T
authors.lastname: Boettler
authors.forename: Friedrich
authors.initials: F
authors.lastname: Moeckel
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Maximilian
authors.initials: M
authors.lastname: Heeg
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
mesh_terms: D000208:Acute Disease; D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002522:Chlorocebus aethiops; D018858:Germinal Center / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053262:Receptors, OX40 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D017735:Virus Latency / Q000276:immunology / Q000502:physiology
chemical_list: D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse