IL-15 activated CD122 triggers Jnk and Akt to regulate motility of effector CD8 T cells

Effector CD8 T cells (CD8 Teff) are key mediators of pathogen clearance, but must migrate to the site of infection to be most effective. We previously reported that IL-15 could induce chemotaxis of CD8 Teff after influenza infection, although how IL-15 signaling mediated migration, and whether this feature was specific to influenza was unclear. We reveal that IL-15 induces CD8 Teff independently of the infection from which they were derived or their state of effector differentiation. Moreover, chemotaxis to IL-15 requires signaling through CD122, but not CD132 or IL-15R, and is dependent on Jak1 activation of PI3K and MAPK cascades. Additionally, we show that IL-15-induced migration of CD8 Teff utilizes heterotrimeric G-protein signaling, suggesting involvement of G-protein signaling downstream of the IL-15 receptor. Together, these data postulate that IL-15-driven CD8 Teff motility requires specific signaling cascades distinct from the proliferative and survival functions of IL-15.