title: TGF-β blockade does not improve control of an established persistent viral infection.
abstract: Acute resolving viral infections are often associated with a strong and multi-specific T-cell response, whereas in persistent viral infections T-cell responses are often impaired. It has been suggested that the resuscitation of the antiviral T-cell response could be a powerful tool to target persisting viruses. Several immunoregulatory pathways, such as IL-10 and TGF-β, have been shown to be involved in the induction of T-cell exhaustion and viral persistence. In this study, we sought to investigate whether TGF-β signaling is also relevant in the maintenance of T-cell exhaustion after viral persistence has been established, and whether blockade of TGF-β signaling could improve control of viral replication in a mouse model of persistent virus infection. Using the LCMV clone 13 model, we analyzed the frequency, function, and phenotype of virus-specific CD4 and CD8 T cells following therapeutic TGF-β signaling blockade. We show that in vivo blockade of the TGF-β receptor failed to substantially enhance the antiviral T-cell response, and was insufficient to mediate a therapeutically-relevant reduction of viral titers in different tissues. Thus, although TGF-β signaling has the ability to hamper antiviral immunity, its pharmacological blockade may not be sufficient to tackle persistent viruses.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Boettler
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Katrin
authors.initials: K
authors.lastname: Ehrhardt
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta