Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets

<jats:p> Natural killer (NK) cells are known to reject MHC-mismatched targets within blood organs, yet their role in peripheral lymphoid tissue remains unresolved. Here we address the capacity of NK cells to migrate within lymph nodes (LN) using two-photon microscopy to characterize cell velocities and interaction dynamics within the native lymphoid-tissue environment. Adoptively transferred unmanipulated NK cells were highly motile (6–7 μm/min) and capable of forming transient contacts with both syngeneic and allogeneic B cells. Stable conjugate interactions (lasting >5 min) formed preferentially with allogeneic cells, resulting in diminished motility and subsequent elimination of the target cell. In marked contrast to unmanipulated cells, NK cells purified by CD49b-positive selection exhibited only limited motility (2–3 μm/min). This velocity impairment arose largely because CD49b cross-linking enhanced NK cell adhesion to collagen fibers within the node. Moreover, CD49b cross-linking prevented NK cells from reconstituting effector cytolytic function <jats:italic>in vivo</jats:italic> , inhibited target cell lysis <jats:italic>in vitro</jats:italic> , and augmented IFN-γ responses to IL-2 activation <jats:italic>in vitro</jats:italic> . Taken together our data demonstrate that NK cells are a functionally important component of the LN microenvironment, and that cell motility and effector function are strongly modulated via CD49b manipulation. </jats:p>