Multiple Deficiencies Underlie NK Cell Inactivity in Lymphotoxin-α Gene-Targeted Mice

Abstract

We have evaluated the NK cell antitumor activity in lymphotoxin (LT)-deficient mice. Both NK cell-mediated tumor rejection and protection from experimental metastases were significantly compromised in LT-α-deficient mice. Analysis of LT-α-deficient mice revealed that the absolute number of αβTCR− NK1.1+ NK cells was reduced in bone marrow and thymus, but with overall proportional decreases in other hemopoietic organs. In addition, the antitumor potential of αβTCR− NK1.1+ cells, as determined by their lytic capacity and perforin expression, was reduced 1.5- to 3-fold in LT-α-deficient mice, as compared with wild-type mice. Combined defects in NK cell development and effector function contribute to compromised NK cell antitumor function in LT-α-deficient mice.