TGF-β Blockade Does Not Improve Control of an Established Persistent Viral Infection

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-beta, 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-beta signaling is also relevant in the maintenance of T-cell exhaustion after viral persistence has been established, and whether blockade of TGF-beta 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-beta signaling blockade. We show that in vivo blockade of the TGF-beta 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-beta signaling has the ability to hamper antiviral immunity, its pharmacological blockade may not be sufficient to tackle persistent viruses.