Relationship between NK cells and granulomatous inflammation in mice

The relationship between natural killer (NK) cells and granulomatous inflammation was investigated using two experimental granuloma models in C57BL/6 mice. The hepatic granuloma model was produced by infection with Schistosoma mansoni (S. mansoni), and the skin granuloma model was established by subcutaneous inoculation of the isolated hepatic granulomas. NK cell activity in lymph nodes and spleen, measured by 51Cr-release assay against YAC-1 cells, was compared to that in age-matched control mice. The activity decreased progressively as granulomas developed without changing the number of NK-1.1+ cells. The reduced NK cell activity was not reversed by administration of indomethacin. In order to further substantiate whether NK cells contribute to granulomatous inflammation, NK cells were depleted in the mice by injection of anti-NK-1.1 mAb. Reduction of NK cell activity (70-90%) was achieved during granuloma formation. An increase of about 20% in the mean granuloma diameter was detected in the mAb-treated mice in both models. Moreover, the percentage of granuloma takes in the skin model was enhanced (65% increase). The mAb treatment did not alter T cell counts in granulomas, T cell subset numbers or proliferative response in spleen. These findings indicate that NK cells directly play a regulatory role in granulomatous inflammation.