MIP-1α, MIP-1β, RANTES, and ATAC/lymphotactin function together with IFN-γ as type 1 cytokines

Abstract

We analyzed for the first time the expression of chemokines in subpopulations of the murine immune system at the single-cell level. We demonstrate in vitro and in a model of murine listeriosis that macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted (RANTES), and activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin are cosecreted to a high degree with IFN-γ by activated individual natural killer (NK), CD8+T, and CD4+T helper 1 (Th1) cells. Functionally, ATAC and the CC chemokines cooperate with IFN-γ in the up-regulation of CD40, IL-12, and tumor necrosis factor-α, molecules playing a central role in the effector phase of macrophages. Our data indicate that (i) MIP-1α, MIP-1β, RANTES, and ATAC are not only chemoattractants but also coactivators of macrophages, (ii) MIP-1α, MIP-1β, RANTES, and ATAC constitute together with IFN-γ a group of “type 1 cytokines,” and (iii) these cytokines act together as a functional unit that is used by NK cells in the innate phase and then “handed over” to CD8+T cells in the antigen-specific phase of the immune defense, thus bridging the two components of a Th1 immune reaction.