Murine lymph node natural killer cells: regulatory mechanisms of activation or suppression

The kinetics and organ distribution patterns of lymph node natural killer (NK) cell activation or suppression were found to vary according to the type, dose, and route of administration of Corynebacterium parvum or polyinosinic-polycytidylic acid (poly I . poly C). Activation of lymph node NK cells by local injections of C. parvum into the footpad or the peritoneum was restricted to the regional lymph nodes; contralateral and distant lymph nodes were not involved. This selectivity persisted even though splenic and peripheral blood NK cells were strongly activated by the same treatment. Conversely, poly I . poly C induced systemic activation of NK cells without selectively activating the regional lymph nodes. The decline of NK cell activity observed 2 weeks after C. parvum treatment was associated with a state of unresponsiveness to a second injection of NK cell stimulants. The expression of C. parvum-induced suppression could be systemic or restricted to the regional lymph nodes. Possible mechanisms for the anatomical compartmentaliztion of NK cell activation or suppression and the implications for the control of tumor growth and dissemination in vivo are discussed.