IFN-lambda (IFN-λ) induces an antiviral state in many cell types and may contribute to the overall inflammatory environment following infection. Either of these effects may influence adaptive immune responses, but the role of type-3 interferons in the development of primary and memory T cell responses to infection has not been evaluated. Herein, we examined T cell responses to acute or persistent lymphocytic choriomeningitis virus (LCMV) infection in IFN-λR1-deficient mice. Following acute infection, we find that IFN-λR1-deficient mice produced normal levels of interferon, robust NK cell responses, but greater than normal CD4+ and CD8+ T cell responses compared to WT Balb/c mice. There were more T cells that were IL-7Rhi and, correspondingly, the IFN-λR-deficient mice showed a 2–3-fold increase in memory T cell number. The inhibitory effect of IFN-λR expression was independent of direct cytokine signaling into T cells. In contrast to acute infection, the IFN-λR-deficient mice generated markedly diminished T cell responses and had greater weight loss compared to WT mice when confronted with a highly disseminating variant of LCMV. These data indicate that IFN-λR limits T cell responses and memory following transient infection but augments T cell responses during persisting infection. Thus, the immune regulatory functions for IFN-λR are complex and vary with the overall inflammatory environment
