CD4(+) T cell help and innate-derived IL-27 induce Blimp-1 dependent IL-10 production by anti-viral CTL

IL-10 is an important regulatory cytokine which can modulate excessive immune mediated injury. Several distinct cell types have been demonstrated to produce IL-10 including most recently CD8(+) cytotoxic T lymphocytes (CTL) responding to respiratory virus infection. Here we report that CD4(+) T cell help in the form of IL-2 is required for IL-10 production by CTL, but not for the induction of CTL effector cytokines. We show that IL-2 derived from CD4(+) T(H) cells cooperates with innate-derived IL-27 to amplify IL-10 production by CTL through a Blimp-1 dependent mechanism. These findings reveal a previously unrecognized pathway that coordinates signals derived from both innate and T(H) cells to control the production of a regulatory cytokine by CTL during acute viral infection.