IL-10 blockade resurrects T cell activity and eliminates a persistent viral infection

By definition persistent viral infections are accompanied by immune evasion, and most notably the failure to sustain robust T cell responses, responses that are essential to control of these infections. Identifying and understanding the immunoregulatory mechanisms that direct productive versus abortive T cell responses to viral infections is critical, but currently unclear. Using the model of persistent lymphocytic choriomeningitis virus (LCMV) infection, we found that upregulation of interleukin (IL)-10 early during infection induces T cell exhaustion and directly leads to viral persistence. Blockade of IL-10 activity induced sustained T cell function, the rapid elimination of an otherwise persistent virus infection and development of functional memory T cells capable of preventing re-infection. Antibody blockade of the IL-10 receptor during the chronic phase of infection restored T cell activity and eliminated an established persistent viral infection. Further, by manipulating this immunoregulatory molecule we significantly enhance immune responses to vaccination, indicating a potential “adjuvant” role to anti-IL10 immunotherapy. Thus, we propose a novel therapy to treat persistent viral infection by targeting host immunoregulatory molecules and reactivating antiviral T cells.