CD8 T cells are recruited to inflamed tissue independent of their antigen specificity, but whether CD8 T cells with irrelevant specificities contribute to the immune response is unclear. We found that Lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells from a previous LCMV infection were recruited in large numbers to leishmanial lesions in mice infected with L. major. Importantly, LCMV immune mice developed larger leishmanial lesions than naïve mice, associated with increased CD8 T cell, neutrophil and monocyte infiltration into the lesions. The recruited CD8 T cells produced granzyme B and increased levels of circulating granzyme B were detected in the serum of LCMV immune mice that had been challenged with L. major, suggesting that granzyme B may be promoting the increased inflammation. This prompted us to determine what cytokines might stimulate the production of granzyme B from previously activated CD8 T cells in the absence of T cell receptor signaling. We found that IL-15 induced granzyme B, but not IFN-γ, expression. In contrast, IL-12 + IL-18 induced IFN-γ but little granzyme B expression. Thus, our findings demonstrate that bystander CD8 T cells can influence the outcome of subsequent infections, and that the cytokine milieu may dictate how the bystander memory CD8 T cells respond within inflamed sites.
- Copyright © 2013 by The American Association of Immunologists, Inc.