Resolution of a chronic viral infection after interleukin-10 receptor blockade

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon.. production by antiviral CD8(+) T cells was enhanced. In persistently infected mice, CD8 alpha(+) dendritic cell (DC) numbers declined early after infection, whereas CD8 alpha(-) DC numbers were not affected. CD8 alpha(-) DCs supported IL- 10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-IOR blockade broke the cycle of IL-10 mediated immune suppression, preventing IL-10 priming by CD8 alpha(-) DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.