Regulation of human natural killer cell migration and proliferation by theexodus subfamily of CC chemokines

Natural killer (NR) cells play an important role in innate and adaptive imm une responses to obligate intracellular pathogens. Nevertheless, the regula tion of NK cell trafficking and migration to inflammatory sites is poorly u nderstood. Exodus-1/MIP-3 alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP -3 beta/ELC/CK beta-11 are CC chemokines that share a unique aspartate-cyst eine-cysteine-leucine motif near their amino terminus and preferentially st imulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectab le chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 a nd -3 stimulated migration of polyclonal activated peripheral blood NK cell s in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Ex odus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodu s-1, -2, and -3 did not induce NK; cell proliferation in the absence of oth er stimuli. Nevertheless, Exodus-2 and -3 significantly augmented ILS-induc ed proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-l, -2, and -3 did not affect the cytolytic activity of resting or activated p eripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NH cells and NRL cells but not resting NK cells. Taken together, these results indicate tha t Exodus-2 and -3 can participate in the recruitment and proliferation of a ctivated NH cells. Exodus-2 and -3 may regulate interactions between T cell s and NK cells that are crucial for the generation of optimal immune respon ses, (C) 2000 Academic Press.