Multiple deficiencies underlie NK cell inactivity in lymphotoxin-α gene knockout 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-{alpha}-deficient mice. Analysis of LT-{alpha}-deficient mice revealed that the absolute number of {alpha}{beta}TCR- 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 {alpha}{beta}TCR- NK1.1+ cells, as determined by their lytic capacity and perforin expression, was reduced 1.5- to 3-fold in LT-{alpha}-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-{alpha}-deficient mice. Combined defects in NK cell development and effector function contribute to compromised NK cell antitumor function in LTa- deficient mice.