Mechanism of NK cell activation: relationship between Qa5+ NK cells and lymphocytes.

Interferon (IF) induces within 20 hr of incubation Qa5+Thy-1- NK cells but Qa5-Thy-1+ cytotoxic cells in cultures of murine splenocytes. The mechanism of Qa5+ NK cell activation has been studied by using tumor necrosis serum (TNS), concanavalin A (Con A), and lipolysaccharide (LPS) as additional NK cell-inducing reagents. It was found that IF and TNS activate precursor NK cells directly without the involvement of accessory cells. The T cell mitogen Con A and the B cell mitogen LPS, on the other hand, induced Qa5+ NK cells only in the presence of lymphocytes. Con A-stimulated T cells and LPS-stimulated B cells release factors into the culture medium that activate Qa5+ NK cells. Since Con A and LPS are known to be interferon inducers, it is inferred that Con A-induced and LPS-induced activation of NK cells is mediated by IF. The data demonstrate that NK cells become activated as a consequence of lymphocyte activation and thus suggest a relationship between lymphocyte dependent- and NK cell-dependent defense systems. This relationship is also implied by observations made with NZB mice. NZB mice lose NK cell activity at the time when they develop autoimmune diseases.