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

Interferon (IF) induces within 20 hr of incubation of Qa5⁺Thy-1^- NK cells but not 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 lipopolysaccharide (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.